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Yildiz Gulhan P, Eroz R, Ozturk CE, Yekenkurul D, Altinsoy HB, Gulec Balbay E, Ercelik M, Davran F, Yildiz S. Determination of both the expression and serum levels of epidermal growth factor and transforming growth factor β1 genes in COVID-19. Sci Rep 2025; 15:9771. [PMID: 40118922 PMCID: PMC11928509 DOI: 10.1038/s41598-025-92304-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2024] [Accepted: 02/26/2025] [Indexed: 03/24/2025] Open
Abstract
We aimed to evaluate the effects of both the expression and serum levels of Epidermal growth factor (EGF) and Transforming growth factor-β1 (TGF-β1) genes in patients with different degrees of cellular damage as mild, moderate, severe, and critical illness that can lead to fibrosis caused by SARS-CoV-2. Totally 45 individuals (male: 21(46.67%); female: 24(53.33%)) with COVID-19 infection were included in this study. Four groups were constituted as mild (n = 16)], moderate (n = 10), severe (n = 10), and critical (n = 9) according to the severity of the disease. Blood samples were drawn from the patients, and all of the hemograms, EGF and TGFβ1 gene expression, and serum levels were evaluated. The mean age of individuals was 57.311 ± 18.383 (min: 28, max: 94). Significant differences were found among the groups for PLT (χ2 = 9.955; p = 0.019), CRP (χ2 = 7.693; p = 0.053), Ferritin (χ2 = 22.196; p < 0.001), D-dimer (χ2 = 21.982; p = 0.000), LDH (χ2 = 21.807; p < 0.001) and all these parameters (exclude PLT in severe groups) was increased depending on the severity of the disease. Additionally, significant differences were detected for EGF (χ2 = 29.528; p < 0.001), TGFB1 (χ2 = 28.981; p < 0.001) expression (that increased depending on the disease severity), and EGF (χ2 = 7.84; p = 0.049), TGFB1 (χ2 = 17.451; p = 0.001) serum concentration levels (that decreased depending on the disease severity). This study found statistically significant differences for both EGF 2-ΔΔCt. TGFβ1 2-ΔΔCt and EGF, TGFβ1 serum concentration values among all patient groups. As disease severity increased, EGF 2-ΔΔCt. TGFβ1 2-ΔΔCt levels increased, while EGF and TGFβ1 serum concentration levels decreased. Perhaps this study will be useful in managing COVID-19 infection severity and pulmonary fibrosis cases secondary to COVID-19.
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Affiliation(s)
- Pinar Yildiz Gulhan
- Department of Chest Diseases, Faculty of Medicine, Duzce University, Konuralp Campus, 81010, Duzce, Turkey.
| | - Recep Eroz
- Department of Medical Genetics, Aksaray University Medical Faculty, Aksaray, Turkey
| | | | - Dilek Yekenkurul
- Department of Infection Diseases, Duzce University Medical Faculty, Duzce, Turkey
| | | | - Ege Gulec Balbay
- Department of Chest Diseases, Faculty of Medicine, Duzce University, Konuralp Campus, 81010, Duzce, Turkey
| | - Merve Ercelik
- Department of Chest Diseases, Faculty of Medicine, Duzce University, Konuralp Campus, 81010, Duzce, Turkey
| | - Fatih Davran
- Department of Biochemistry, Faculty of Medicine, Duzce University, Duzce, Turkey
| | - Seyma Yildiz
- Deparment of Hematology, Gazi University, Ankara, Turkey
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Iroungou BA, Nze O A, M Kandet Y H, Longo-Pendy NM, Mezogho-Obame ND, Dikoumba AC, Mangouka GL. Interest of D-dimer level, severity of COVID-19 and cost of management in Gabon. World J Crit Care Med 2025; 14:100486. [DOI: 10.5492/wjccm.v14.i1.100486] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2024] [Revised: 10/02/2024] [Accepted: 10/30/2024] [Indexed: 12/11/2024] Open
Abstract
BACKGROUND Coronavirus disease 2019 (COVID-19) is strongly associated with an increased risk of thrombotic events, including severe outcomes such as pulmonary embolism. Elevated D-dimer levels are a critical biomarker for assessing this risk. In Gabon, early implementation of anticoagulation therapy and D-dimer testing has been crucial in managing COVID-19. This study hypothesizes that elevated D-dimer levels are linked to increased COVID-19 severity.
AIM To determine the impact of D-dimer levels on COVID-19 severity and their role in guiding clinical decisions.
METHODS This retrospective study analyzed COVID-19 patients admitted to two hospitals in Gabon between March 2020 and December 2023. The study included patients with confirmed COVID-19 diagnoses and available D-dimer measurements at admission. Data on demographics, clinical outcomes, D-dimer levels, and healthcare costs were collected. COVID-19 severity was classified as non-severe (outpatients) or severe (inpatients). A multivariable logistic regression model was used to assess the relationship between D-dimer levels and disease severity, with adjusted odds ratios (OR) and 95%CI.
RESULTS A total of 3004 patients were included, with a mean age of 50.17 years, and the majority were female (53.43%). Elevated D-dimer levels were found in 65.81% of patients, and 57.21% of these experienced severe COVID-19. Univariate analysis showed that patients with elevated D-dimer levels had 3.33 times higher odds of severe COVID-19 (OR = 3.33, 95%CI: 2.84-3.92, P < 0.001), and this association remained significant in the multivariable analysis, adjusted for age, sex, and year of collection. The financial analysis revealed a substantial burden, particularly for uninsured patients.
CONCLUSION D-dimer predicts COVID-19 severity and guides treatment, but the high cost of anticoagulant therapy highlights the need for policies ensuring affordable access in resource-limited settings like Gabon.
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Affiliation(s)
- Berthe A Iroungou
- Unité Mixte de Recherche, Centre International de Recherches Médicales de Franceville et le Service de Santé Militaire, Libreville 20404, Estuaire, Gabon
| | - Arnaud Nze O
- AP-HP Health Economics, Research Unit, Htel Dieu Hospital, Paris 75004, Ile-de-France, France
| | - Helga M Kandet Y
- Laboratory, Hôpital D'Instruction des Armées D'Akanda, Libreville 20404, Estuaire, Gabon
| | - Neil-Michel Longo-Pendy
- Unité de Recherche en Écologie de la Santé, Centre Interdisciplinaire de Recherches Médicales de Franceville, Franceville 769, Gabon
| | - Nina D Mezogho-Obame
- Laboratory, Hôpital D'Instruction des Armées Omar Bongo Ondimba, Libreville 20404, Estuaire, Gabon
| | - Annicet-Clotaire Dikoumba
- Unité Mixte de Recherche, Centre International de Recherches Médicales de Franceville et le Service de Santé Militaire, Libreville 20404, Estuaire, Gabon
| | - Guignali L Mangouka
- Department of Medecine Polyvalente, Hôpital D'Instruction des Armées Omar Bongo Ondimba, Libreville 20404, Estuaire, Gabon
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Zhu W, Zheng Y, Yu M, Witman N, Zhou L, Wei J, Zhang Y, Topchyan P, Nguyen C, Wang D, Janecke R, Padmanabhan A, Baumann Kreuziger L, White GC, Hari P, Gu T, Fields AT, Kornblith LZ, Aster R, Zhu J, Cui W, Jobe S, Graham MB, Wang D, Wen R. Prothrombotic antibodies targeting the spike protein's receptor-binding domain in severe COVID-19. Blood 2025; 145:635-647. [PMID: 39576992 PMCID: PMC11811936 DOI: 10.1182/blood.2024025010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2024] [Revised: 10/21/2024] [Accepted: 11/06/2024] [Indexed: 11/24/2024] Open
Abstract
ABSTRACT Thromboembolic complication is common in severe coronavirus disease 2019 (COVID-19), leading to an investigation into the presence of prothrombotic antibodies akin to those found in heparin-induced thrombocytopenia (HIT). In a study of samples from 130 hospitalized patients, collected 3.6 days after COVID-19 diagnosis, 80% had immunoglobulin G (IgG) antibodies recognizing complexes of heparin and platelet factor 4 (PF4; PF4/H), and 41% had antibodies inducing PF4-dependent P-selectin expression in CpG oligodeoxynucleotide-treated normal platelets. Unlike HIT, both PF4/H-reactive and platelet-activating antibodies were found in patients with COVID-19 regardless of recent heparin exposure. Notably, PF4/H-reactive IgG antibodies correlated with those targeting the receptor-binding domain (RBD) of the severe acute respiratory syndrome coronavirus 2 spike protein. Moreover, introducing exogenous RBD to or removing RBD-reactive IgG from COVID-19 plasma or IgG purified from COVID-19 plasma significantly reduced their ability to activate platelets. RBD-specific antibodies capable of platelet activation were cloned from peripheral blood B cells of patients with COVID-19. These antibodies possessed sequence motifs in the heavy-chain complementarity-determining region 3 (HCDR3), resembling those identified in pathogenic HIT antibodies. Furthermore, IgG+ B cells having these HCDR3 signatures were markedly expanded in patients with severe COVID-19. Importantly, platelet-activating antibodies present in patients with COVID-19 were associated with a specific elevation of platelet α-granule proteins in the plasma and showed a positive correlation with markers for inflammation and tissue damage, suggesting a functionality of these antibodies in patients. The demonstration of functional and structural similarities between certain RBD-specific antibodies in patients with COVID-19 and pathogenic antibodies typical of HIT suggests a novel mechanism by which RBD-specific antibodies might contribute to thrombosis in COVID-19.
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Affiliation(s)
- Wen Zhu
- Versiti Blood Research Institute, Milwaukee, WI
- Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI
| | | | - Mei Yu
- Versiti Blood Research Institute, Milwaukee, WI
| | - Nathan Witman
- Versiti Blood Research Institute, Milwaukee, WI
- Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI
| | - Lu Zhou
- Versiti Blood Research Institute, Milwaukee, WI
- Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI
| | - Jianhui Wei
- Versiti Blood Research Institute, Milwaukee, WI
- Biomedical Research Center of South China, College of Life Sciences, Fujian Normal University, Fuzhou, China
| | - Yongguang Zhang
- Versiti Blood Research Institute, Milwaukee, WI
- Biomedical Research Center of South China, College of Life Sciences, Fujian Normal University, Fuzhou, China
| | - Paytsar Topchyan
- Versiti Blood Research Institute, Milwaukee, WI
- Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI
| | - Christine Nguyen
- Versiti Blood Research Institute, Milwaukee, WI
- Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI
| | - David Wang
- School of Art and Science Undergraduate Program, Washington University in St. Louis, St. Louis, MO
| | - Rae Janecke
- Versiti Blood Research Institute, Milwaukee, WI
| | - Anand Padmanabhan
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN
| | - Lisa Baumann Kreuziger
- Versiti Blood Research Institute, Milwaukee, WI
- Division of Hematology Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI
| | | | - Parameswaran Hari
- Division of Hematology Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI
| | - Tongjun Gu
- Versiti Blood Research Institute, Milwaukee, WI
| | - Alexander T. Fields
- Department of Surgery, University of California San Francisco, San Francisco, CA
| | - Lucy Z. Kornblith
- Department of Surgery, University of California San Francisco, San Francisco, CA
- Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA
| | - Richard Aster
- Versiti Blood Research Institute, Milwaukee, WI
- Division of Hematology Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI
| | - Jieqing Zhu
- Versiti Blood Research Institute, Milwaukee, WI
- Department of Biochemistry, Medical College of Wisconsin, Milwaukee, WI
| | - Weiguo Cui
- Versiti Blood Research Institute, Milwaukee, WI
- Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI
- Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL
| | - Shawn Jobe
- Versiti Blood Research Institute, Milwaukee, WI
- Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, East Lansing, MI
| | - Mary Beth Graham
- Division of Infectious Disease, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI
| | - Demin Wang
- Versiti Blood Research Institute, Milwaukee, WI
- Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI
| | - Renren Wen
- Versiti Blood Research Institute, Milwaukee, WI
- Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI
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Sukati S, Kotepui KU, Masangkay FR, Tseng CP, Mahittikorn A, Anabire NG, Wilairatana P, Wangdi K, Majima HJ, Suwannatrai AT, Klangbud WK, Mala W, Rattanatham R, Kotepui M. Elevations in D-dimer levels in patients with Plasmodium infections: a systematic review and meta-analysis. Sci Rep 2025; 15:858. [PMID: 39757238 PMCID: PMC11701129 DOI: 10.1038/s41598-024-84907-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2024] [Accepted: 12/30/2024] [Indexed: 01/07/2025] Open
Abstract
D-dimer, a byproduct of cross-linked fibrin degradation, arises during the fibrinolysis process, breaking down blood clots in circulation. This systematic review and meta-analysis aimed to synthesize evidence of D-dimer alteration in people with malaria, including variations in disease severity. The systematic review was registered in PROSPERO with registration number CRD42024528245. Searches were performed in EMBASE, Scopus, MEDLINE, PubMed, Nursing & Allied Health Premium, and Journals@Ovid on March 25, 2024, to identify original studies that reported D-dimer in patients with Plasmodium infections. The methodological quality of the included studies was assessed using the Joanna Briggs Institute critical appraisal tools. Thematic synthesis and meta-analysis were carried out to synthesize the findings of the included studies. A total of 24 studies were included in the review out of 1,115 records identified. According to the evaluated studies, patients with Plasmodium infections had higher D-dimer levels. A meta-analytic evaluation of D-dimer levels between patients with and without Plasmodium infections revealed a significant elevation of D-dimer in patients with infection, with high heterogeneity (SMD = 2.11, 95% CI = 0.59; 3.64, P = 0.007, I² = 98%, 6 studies, 1,418 participants, random-effects model). However, no significant alterations in D-dimer levels were observed following the comparison between patients with severe and uncomplicated malaria, also with high heterogeneity (SMD = 2.54, 95% CI = -1.60; 6.68, P = 0.23, I² = 99%, 3 studies, 595 participants). The findings suggested that malaria patients have significantly higher D-dimer levels compared to non-malarial individuals. However, there was no significant difference in D-dimer levels between severe and uncomplicated malaria cases. These results highlight the potential of D-dimer as a biomarker for Plasmodium infections, but its clinical utility requires further validation. Future studies should prioritize standardizing D-dimer measurement methods, including assay types, threshold values, and sample types, to ensure consistent and reliable application in clinical settings. Additionally, large, multicentric cohorts are needed to establish robust guidelines for incorporating D-dimer into malaria management practices. Further research should also explore the role of D-dimer in the pathogenesis of Plasmodium infections to deepen our understanding of their clinical significance.
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Affiliation(s)
- Suriyan Sukati
- Medical Technology, School of Allied Health Sciences, Walailak University, Tha Sala, Nakhon Si Thammarat, Thailand
- Hematology and Transfusion Science Research Center, Walailak University, Tha Sala, Nakhon Si Thammarat, Thailand
| | | | | | - Ching-Ping Tseng
- Graduate Institute of Biomedical Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Department of Laboratory Medicine, Linkou Branch, Chang Gung Memorial Hospital, Taoyuan, Taiwan
- Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Aongart Mahittikorn
- Department of Protozoology, Faculty of Tropical Medicine, Mahidol University, Bangkok, 10400, Thailand
| | - Nsoh Godwin Anabire
- Department of Biochemistry & Molecular Medicine, School of Medicine, University for Development Studies, Tamale, Ghana
- West African Centre for Cell Biology of Infectious Pathogens (WACCBIP), Department of Biochemistry, Cell & Molecular Biology, University of Ghana, Accra, Ghana
| | - Polrat Wilairatana
- Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, 10400, Thailand
| | - Kinley Wangdi
- HEAL Global Research Centre, Health Research Institute, Faculty of Health, University of Canberra, Canberra, Australia, ACT, 2617, Kirinari Street
- National Centre for Epidemiology and Population Health, Australian National University, Canberra, Australia, 62 Mills Road, ACT, 2601
| | - Hideyuki J Majima
- Medical Technology, School of Allied Health Sciences, Walailak University, Tha Sala, Nakhon Si Thammarat, Thailand
| | | | - Wiyada Kwanhian Klangbud
- Medical Technology Program, Faculty of Science, Nakhon Phanom University, Nakhon Phanom, Thailand
| | - Wanida Mala
- Medical Technology Program, Faculty of Science, Nakhon Phanom University, Nakhon Phanom, Thailand
| | - Rujikorn Rattanatham
- Medical Technology Program, Faculty of Science, Nakhon Phanom University, Nakhon Phanom, Thailand
| | - Manas Kotepui
- Medical Technology Program, Faculty of Science, Nakhon Phanom University, Nakhon Phanom, Thailand.
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Arientová S, Matúšková K, Bartoš O, Beran O, Holub M. Evaluation of Soluble Urokinase Plasminogen Activator Receptor in COVID-19 Patients. J Clin Med 2024; 13:6340. [PMID: 39518479 PMCID: PMC11546495 DOI: 10.3390/jcm13216340] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Revised: 10/04/2024] [Accepted: 10/21/2024] [Indexed: 11/16/2024] Open
Abstract
Background/Objectives: This retrospective study analyzed soluble urokinase plasminogen activator receptor (suPAR) plasma levels alongside routine inflammatory markers, including the neutrophil-to-lymphocyte count ratio, C-reactive protein (CRP), interleukin-6 (IL-6), procalcitonin (PCT), and D-dimers in COVID-19 patients hospitalized during the Omicron wave of the pandemic. Methods: We measured plasma suPAR levels using a suPARnostic® Quick Triage kit. We divided COVID-19 patients into two groups based on the severity of SARS-CoV-2 infection according to the National Institutes of Health (NIH) criteria. The logistic regression analysis tested the predictive value of the biomarkers. Results: We evaluated 160 consecutive COVID-19 patients hospitalized between January and August 2022. The cohort exhibited a high incidence of comorbidities, with an in-hospital mortality rate of 5.6%. Upon admission, the median suPAR plasma levels were not significantly different between patients with mild COVID-19 (n = 110) and those with moderate/severe disease (n = 50), with 7.25 ng/mL and 7.55 ng/mL, respectively. We observed significant differences (p < 0.01) between the groups for CRP and IL-6 levels that were higher in moderate/severe disease than in mild infection. Additionally, suPAR plasma levels were above the normal range (0-2.00 ng/mL) in all patients, with a significant positive correlation identified between suPAR levels and serum IL-6, PCT, and creatinine levels. Conclusions: These findings indicate that COVID-19 during the Omicron wave is strongly associated with elevated suPAR levels; however, these levels do not directly correlate with the severity of SARS-CoV-2 infection.
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Affiliation(s)
- Simona Arientová
- Department of Infectious Diseases, Military University Hospital Prague and First Faculty of Medicine of Charles University, 16902 Prague, Czech Republic; (S.A.); (K.M.); (O.B.)
| | - Kateřina Matúšková
- Department of Infectious Diseases, Military University Hospital Prague and First Faculty of Medicine of Charles University, 16902 Prague, Czech Republic; (S.A.); (K.M.); (O.B.)
| | - Oldřich Bartoš
- Military Health Institute, Military Medical Agency, 16200 Prague, Czech Republic
| | - Ondřej Beran
- Department of Infectious Diseases, Military University Hospital Prague and First Faculty of Medicine of Charles University, 16902 Prague, Czech Republic; (S.A.); (K.M.); (O.B.)
| | - Michal Holub
- Department of Infectious Diseases, Military University Hospital Prague and First Faculty of Medicine of Charles University, 16902 Prague, Czech Republic; (S.A.); (K.M.); (O.B.)
- Ústřední Vojenská Nemocnice—Vojenská Fakultní Nemonice Praha, U Vojenské Nemocnice 1200, Praha 6-Břevnov, 16902 Prague, Czech Republic
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Kattainen S, Pitkänen H, Reijula J, Hästbacka J. Complete blood count, coagulation biomarkers, and lung function 6 months after critical COVID-19. Acta Anaesthesiol Scand 2024; 68:940-948. [PMID: 38723274 DOI: 10.1111/aas.14437] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2023] [Revised: 04/11/2024] [Accepted: 04/21/2024] [Indexed: 07/27/2024]
Abstract
BACKGROUND Understanding the recovery of post-COVID-19 organ dysfunction is essential. We evaluated coagulation 6 months post-COVID-19, examining its recovery and association with lung function. METHODS Patients treated for COVID-19 at intensive care units between 3/2020 and 1/2021 were analyzed for complete blood count (CBC) and coagulation biomarkers (prothrombin time activity (%) (PT%), activated partial thromboplastin time (APTT), fibrinogen, coagulation factor VIII (FVIII), antithrombin (AT), and D-dimer) during the 6 months post-hospitalization. Results were compared with acute phase values and correlated with pulmonary function tests (PFT), including forced vital capacity (FVC) and hemoglobin-corrected diffusing capacity percentage of predicted (DLCOc%), recorded 6 months post-hospitalization. We examined the association between coagulation biomarkers and DLCOc% using linear regression with age, sex, and invasive mechanical ventilation (IMV) duration, and FVIII (correlated with DLCOc%) as covariates. RESULTS Most CBCs and coagulation biomarkers had median values within the normal range. However, only 21% (15/70) of patients achieved full normalization of all biomarkers. Compared to acute COVID-19, hemoglobin, PT%, and AT increased, while leukocytes, fibrinogen, FVIII, and D-dimer decreased. Despite decreased levels, FVIII remained elevated in 46% (31/68), leukocytes in 26% (18/70), and D-dimer in 27% (18/67) at 6 months. A weak negative correlation (r = -0.37, p = .036) was found between DLCOc% and FVIII. Multivariable analysis revealed a weak, independent association between DLCOc% and FVIII. Excluding patients with anticoagulation therapy, FVIII no longer correlated with DLCOc%, while AT showed a moderate correlation with DLCOc%. CONCLUSION Only a few patients had normal CBC and coagulation biomarker values 6 months after critical COVID-19. A weak negative correlation between DLCOc% and FVIII suggests that deranged coagulation activity may be associated with reduced diffusing capacity.
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Affiliation(s)
- Salla Kattainen
- Division of Intensive Care, Department of Perioperative and Intensive Care Medicine, University of Helsinki and HUS Helsinki University Hospital, Helsinki, Finland
| | - Hanna Pitkänen
- Division of Intensive Care, Department of Perioperative and Intensive Care Medicine, University of Helsinki and HUS Helsinki University Hospital, Helsinki, Finland
| | - Jere Reijula
- Department of Pulmonology, Heart and Lung Center, University of Helsinki and HUS Helsinki University Hospital, Helsinki, Finland
| | - Johanna Hästbacka
- Department of Anaesthesia and Intensive Care, Tampere University Hospital, University of Tampere, Tampere, Finland
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Rettew A, Garrahy I, Rahimian S, Brown R, Sangha N. COVID-19 Coagulopathy. Life (Basel) 2024; 14:953. [PMID: 39202695 PMCID: PMC11355811 DOI: 10.3390/life14080953] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Revised: 07/25/2024] [Accepted: 07/26/2024] [Indexed: 09/03/2024] Open
Abstract
Coronavirus disease of 2019 (COVID-19) is the respiratory viral infection caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite being a primary respiratory illness, it is commonly complicated by systemic involvement of the vasculature leading to arterial and venous thrombosis. In this review, we will focus on the association between COVID-19 and thrombosis. We will highlight the pathophysiology of COVID-19 coagulopathy. The clinical manifestations of COVID-19 vasculopathy will be discussed with a focus on venous and arterial thromboembolic events. COVID-19 vasculopathy and disseminated intravascular coagulation (DIC) are distinguished within, as well as areas of controversy, such as "long COVID". Finally, the current professional guidelines on prevention and treatment of thrombosis associated with SARS-CoV-2 infection will be discussed.
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Affiliation(s)
| | - Ian Garrahy
- Tower Health System, Reading Hospital, West Reading, PA 19611, USA; (A.R.); (S.R.); (R.B.); (N.S.)
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Oncu S, Korkmaz D. Evaluation of the relationship of treatment and vaccination with prognosis in patients with a diagnosis of COVID-19. Inflammopharmacology 2024; 32:1817-1826. [PMID: 38493271 PMCID: PMC11136715 DOI: 10.1007/s10787-024-01457-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2024] [Accepted: 03/01/2024] [Indexed: 03/18/2024]
Abstract
PURPOSE Coronavirus disease 2019 (COVID-19) has affected millions of people worldwide and caused mortality. Many factors have been reported to affect the prognosis of COVID-19. In this study, we aimed to investigate the effects of drug therapy and vaccination on prognosis in patients hospitalized with a COVID-19 diagnosis. METHODS In this single-center, cross-sectional study, data were retrospectively collected from patients receiving inpatient treatment at a university hospital with a diagnosis of COVID-19 between January 1, 2020, and April 30, 2022. The patients' demographic and clinical characteristics were recorded. The Chi-square, Cox and logistic regression was performed, P < 0.05 was considered statistically significant. RESULTS Total 1723 patients (50.1% were men, mean age: 60.6 ± 16.90) who had not been vaccinated rate was 27.0% (> 3 doses: 45.7%). Mortality rate was 17.0%. Increasing age, male, a high Charlson Comorbidity Index (CCI), and no vaccination significantly increased mortality (P < 0.05). The mortality rate was significantly lower in the chloroquine treatment group than in the other treatment groups. Increasing age, male, and a high CCI were determined to be factors that significantly increased the length of hospital stay (LOHS). LOHS found to be significantly lower in the favipiravir or chloroquine groups compared to the remaining treatment groups (P < 0.001). Both mortality and the LOHS significantly differed according to AST, d-dimer, ferritin, and GFR. CONCLUSION This study primarily investigated the effect of treatment and vaccination on the prognosis of COVID-19. This was determined to be prepared for another potential pandemic that may arise due to COVID-19.
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Affiliation(s)
- Seyma Oncu
- Department of Pharmacology, Faculty of Medicine, Afyonkarahisar Health Sciences University, Afyonkarahisar, 03030, Turkey.
| | - Derya Korkmaz
- Department of Infectious Disease, Faculty of Medicine, Afyonkarahisar Health Sciences University, Afyonkarahisar, Turkey
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Fatima J, Shukla V, Siddiqi Z, Kumar D, Mateen S, Gupta AB. Correlation of Serum Calcium with Severity and Outcomes in Patients of COVID-19 Pneumonia. J Family Med Prim Care 2024; 13:1421-1427. [PMID: 38827666 PMCID: PMC11141953 DOI: 10.4103/jfmpc.jfmpc_1595_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2023] [Revised: 12/13/2023] [Accepted: 12/14/2023] [Indexed: 06/04/2024] Open
Abstract
Background Calcium is an essential electrolyte with critical physiological functions. Recently, it has been implicated in the pathogenesis and outcomes of COVID-19. This retrospective study was conducted to estimate serum ionic calcium and its correlation with clinical severity, inflammatory markers, and in-hospital outcomes in moderate to severe COVID-19 patients. Methods We retrospectively analyzed data from 377 COVID-19 patients, aged between 23 and 79 years, with a mean age of 54.17±11.53 years. Severity of the disease was determined using ICMR criteria. Parameters including age, gender, inflammatory markers, calcium levels, and clinical outcomes were assessed. Results The study showed a prevalence of moderate and severe COVID-19 in 58.1% and 41.9% patients, respectively. Severity was significantly associated with younger age, higher mean inflammatory markers, notably IL-6, procalcitonin, D-Dimer, and lower ionic and total calcium levels, as well as vitamin D levels. Mortality and referral rate were significantly higher in the severe group. Hypocalcemia was prevalent in 39% of the patients and was significantly associated with disease severity, ARDS, and mortality. On multivariate assessment, only age and ionic calcium were significantly associated with COVID-19 severity. Conclusion Lower serum ionic calcium levels are associated with increased severity and poor outcomes, including higher mortality in COVID-19 patients, underscoring the potential role of calcium as a diagnostic and prognostic marker in COVID-19 pneumonia and may be an important factor in various other forms of pneumonia.
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Affiliation(s)
- Jalees Fatima
- Department of Medicine, Era’s Lucknow Medical College and Hospital, Lucknow, Uttar Pradesh, India
| | - Vaibhav Shukla
- Department of Medicine, Era’s Lucknow Medical College and Hospital, Lucknow, Uttar Pradesh, India
| | - Zeba Siddiqi
- Department of Medicine, Era’s Lucknow Medical College and Hospital, Lucknow, Uttar Pradesh, India
| | - Devendra Kumar
- Department of Medicine, Era’s Lucknow Medical College and Hospital, Lucknow, Uttar Pradesh, India
| | - Saboor Mateen
- Department of Medicine, Era’s Lucknow Medical College and Hospital, Lucknow, Uttar Pradesh, India
| | - Akhilesh Bandhu Gupta
- Maharishi Markendeshwar College of Medical Science and Research, Ambala, Haryana, India
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10
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Maulidyanti ETS, Purwaningsih NV, Ainutajriani A, Widyastuti R. Impact of Sample Type on D-Dimer Screening. Malays J Med Sci 2024; 31:153-158. [PMID: 38694586 PMCID: PMC11057822 DOI: 10.21315/mjms2024.31.2.13] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2023] [Accepted: 06/29/2023] [Indexed: 05/04/2024] Open
Abstract
Background The quality of laboratory test results depends on various factors, including sample type selection. Blood samples, such as whole blood, plasma and serum are commonly used for most clinical laboratory examinations. D-dimer parameters are frequently analysed in haematology laboratories and serve as biomarkers for coagulation activation and fibrinolysis. This study aimed to assess the impact of using different sample types on the quality of D-dimer test results. Method An observational analytical method was used. D-dimer examination was performed using the fluorescent lateral flow immunoassay method. The study sample consisted of 26 participants aged between 18 years old and 22 years old who had no blood disorders. Whole blood and ethylenediaminetetraacetic acid (EDTA) plasma samples were used for the examination of D-dimer levels. Results D-dimer levels in 26 participants using whole blood samples had a mean value of 0.23 mg/L (230 ng/mL), while plasma samples yielded a mean value of 0.14 mg/L (140 ng/mL). D-dimer levels obtained from whole blood samples were higher than plasma samples but remained within the normal range of 0 mg/L-0.5 mg/L (0 ng/mL-500 ng/mL). Conclusion The results showed that whole blood samples were more practical than plasma samples. Nevertheless, plasma samples gave results within the normal range of D-dimer values.
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Affiliation(s)
- Ellies Tunjung Sari Maulidyanti
- Department of Medical Technology Laboratory, Faculty Health Science, University Muhammadiyah of Surabaya, Surabaya, Indonesia
| | - Nur Vita Purwaningsih
- Department of Medical Technology Laboratory, Faculty Health Science, University Muhammadiyah of Surabaya, Surabaya, Indonesia
| | - Ainutajriani Ainutajriani
- Department of Medical Technology Laboratory, Faculty Health Science, University Muhammadiyah of Surabaya, Surabaya, Indonesia
| | - Rahma Widyastuti
- Department of Medical Technology Laboratory, Faculty Health Science, University Muhammadiyah of Surabaya, Surabaya, Indonesia
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11
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Bader SM, Cooney JP, Sheerin D, Taiaroa G, Harty L, Davidson KC, Mackiewicz L, Dayton M, Wilcox S, Whitehead L, Rogers KL, Georgy SR, Coussens AK, Grimley SL, Corbin V, Pitt M, Coin L, Pickering R, Thomas M, Allison CC, McAuley J, Purcell DFJ, Doerflinger M, Pellegrini M. SARS-CoV-2 mouse adaptation selects virulence mutations that cause TNF-driven age-dependent severe disease with human correlates. Proc Natl Acad Sci U S A 2023; 120:e2301689120. [PMID: 37523564 PMCID: PMC10410703 DOI: 10.1073/pnas.2301689120] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Accepted: 06/13/2023] [Indexed: 08/02/2023] Open
Abstract
The diversity of COVID-19 disease in otherwise healthy people, from seemingly asymptomatic infection to severe life-threatening disease, is not clearly understood. We passaged a naturally occurring near-ancestral SARS-CoV-2 variant, capable of infecting wild-type mice, and identified viral genomic mutations coinciding with the acquisition of severe disease in young adult mice and lethality in aged animals. Transcriptomic analysis of lung tissues from mice with severe disease elucidated a host antiviral response dominated mainly by interferon and IL-6 pathway activation in young mice, while in aged animals, a fatal outcome was dominated by TNF and TGF-β signaling. Congruent with our pathway analysis, we showed that young TNF-deficient mice had mild disease compared to controls and aged TNF-deficient animals were more likely to survive infection. Emerging clinical correlates of disease are consistent with our preclinical studies, and our model may provide value in defining aberrant host responses that are causative of severe COVID-19.
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Affiliation(s)
- Stefanie M. Bader
- The Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC3052, Australia
- Department of Medical Biology, University of Melbourne, Melbourne, VIC3052, Australia
| | - James P. Cooney
- The Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC3052, Australia
- Department of Medical Biology, University of Melbourne, Melbourne, VIC3052, Australia
| | - Dylan Sheerin
- The Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC3052, Australia
- Department of Medical Biology, University of Melbourne, Melbourne, VIC3052, Australia
| | - George Taiaroa
- Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC3000, Australia
| | - Leigh Harty
- Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC3000, Australia
| | - Kathryn C. Davidson
- The Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC3052, Australia
- Department of Medical Biology, University of Melbourne, Melbourne, VIC3052, Australia
| | - Liana Mackiewicz
- The Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC3052, Australia
| | - Merle Dayton
- The Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC3052, Australia
| | - Stephen Wilcox
- The Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC3052, Australia
- Department of Medical Biology, University of Melbourne, Melbourne, VIC3052, Australia
| | - Lachlan Whitehead
- The Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC3052, Australia
- Department of Medical Biology, University of Melbourne, Melbourne, VIC3052, Australia
| | - Kelly L. Rogers
- The Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC3052, Australia
- Department of Medical Biology, University of Melbourne, Melbourne, VIC3052, Australia
| | - Smitha Rose Georgy
- Anatomic Pathology, Melbourne Veterinary School, Faculty of Science, University of Melbourne, Melbourne, VIC3030, Australia
| | - Anna K. Coussens
- The Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC3052, Australia
- Department of Medical Biology, University of Melbourne, Melbourne, VIC3052, Australia
| | - Samantha L. Grimley
- Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC3000, Australia
| | - Vincent Corbin
- Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC3000, Australia
| | - Miranda Pitt
- Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC3000, Australia
| | - Lachlan Coin
- Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC3000, Australia
| | - Raelene Pickering
- Department of Diabetes, Monash University, Central Clinical School, Level 5, Alfred Centre, Melbourne, VIC3004, Australia
| | - Merlin Thomas
- Department of Diabetes, Monash University, Central Clinical School, Level 5, Alfred Centre, Melbourne, VIC3004, Australia
| | - Cody C. Allison
- The Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC3052, Australia
| | - Julie McAuley
- Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC3000, Australia
| | - Damian F. J. Purcell
- Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC3000, Australia
| | - Marcel Doerflinger
- The Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC3052, Australia
- Department of Medical Biology, University of Melbourne, Melbourne, VIC3052, Australia
| | - Marc Pellegrini
- The Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC3052, Australia
- Department of Medical Biology, University of Melbourne, Melbourne, VIC3052, Australia
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12
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Patil S, Acharya A, Gondhali G, Narwade G. Does follow-up D-dimer level help in predicting oxygenation status, ventilatory support requirement, lung fibrosis, and thromboembolic events in coronavirus disease 2019 pneumonia? A prospective observational study in a tertiary care setting in India. Ann Afr Med 2023; 22:286-292. [PMID: 37417015 PMCID: PMC10445714 DOI: 10.4103/aam.aam_47_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2022] [Revised: 10/16/2022] [Accepted: 01/04/2023] [Indexed: 07/08/2023] Open
Abstract
Introduction Coronavirus disease 2019 (COVID-19) pneumonia is a heterogeneous disease with variable effects on lung parenchyma, airways, and vasculature, leading to long-term effects on lung functions. Materials and Methods This multicentric, prospective, observational, and interventional study included 1000 COVID-19 cases confirmed with reverse transcription-polymerase chain reaction. All cases were assessed with high-resolution computed tomography thorax, oxygen saturation, inflammatory marker as D-dimer at the entry point, and follow-up. Age, gender, comorbidity, use of bilevel positive airway pressure/noninvasive ventilation (BiPAP/NIV), and outcome as with or without lung fibrosis as per CT severity were key observations. In selected cases, we have performed lower limb venous Doppler and computed tomography (CT) pulmonary angiography to rule out deep-vein thrombosis (DVT) or pulmonary thromboembolism (PTE) respectively. Statistical analysis is performed by using Chi-square test. Observations and Analysis Age (<50 and >50 years) and gender (male vs. female) has a significant association with D-dimer level (P < 0.00001 and P < 0.010, respectively). CT severity score at the entry point with the D-dimer level has a significant correlation (P < 0.00001). The D-dimer level has a significant association with the duration of illness before hospitalization (P < 0.00001). Comorbidities have a significant association with D-dimer levels (P < 0.00001). D-dimer level has a significant association with oxygen saturation (P < 0.00001). BIPAP/NIV requirement has a significant association with the D-dimer level (P < 0.00001). Timing of BIPAP/NIV requirement during hospitalization has a significant association with D-dimer level (P < 0.00001). Follow-up D-dimer titer during hospitalization as compared to normal and abnormal to entry point level has a significant association with post-COVID lung fibrosis, DVT, and PTE (P < 0.00001). Conclusions D-dimer has documented a very crucial role in COVID-19 pneumonia in predicting the severity of illness and assessing response to treatment during hospitalization, and follow-up titers have a significant role in step-up or step-down interventions in a critical care setting.
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Affiliation(s)
- Shital Patil
- Department of Pulmonary Medicine, MIMSR Medical College, Latur, Maharashtra, India
| | - Abhijit Acharya
- Department of Pathology, MIMSR Medical College, Latur, Maharashtra, India
| | - Gajanan Gondhali
- Department of Internal Medicine, MIMSR Medical College, Latur, Maharashtra, India
| | - Ganesh Narwade
- Department of Pulmonary Medicine, MIMSR Medical College, Latur, Maharashtra, India
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13
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Diray-Arce J, Fourati S, Doni Jayavelu N, Patel R, Maguire C, Chang AC, Dandekar R, Qi J, Lee BH, van Zalm P, Schroeder A, Chen E, Konstorum A, Brito A, Gygi JP, Kho A, Chen J, Pawar S, Gonzalez-Reiche AS, Hoch A, Milliren CE, Overton JA, Westendorf K, Cairns CB, Rouphael N, Bosinger SE, Kim-Schulze S, Krammer F, Rosen L, Grubaugh ND, van Bakel H, Wilson M, Rajan J, Steen H, Eckalbar W, Cotsapas C, Langelier CR, Levy O, Altman MC, Maecker H, Montgomery RR, Haddad EK, Sekaly RP, Esserman D, Ozonoff A, Becker PM, Augustine AD, Guan L, Peters B, Kleinstein SH. Multi-omic longitudinal study reveals immune correlates of clinical course among hospitalized COVID-19 patients. Cell Rep Med 2023; 4:101079. [PMID: 37327781 PMCID: PMC10203880 DOI: 10.1016/j.xcrm.2023.101079] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Revised: 01/31/2023] [Accepted: 05/16/2023] [Indexed: 06/18/2023]
Abstract
The IMPACC cohort, composed of >1,000 hospitalized COVID-19 participants, contains five illness trajectory groups (TGs) during acute infection (first 28 days), ranging from milder (TG1-3) to more severe disease course (TG4) and death (TG5). Here, we report deep immunophenotyping, profiling of >15,000 longitudinal blood and nasal samples from 540 participants of the IMPACC cohort, using 14 distinct assays. These unbiased analyses identify cellular and molecular signatures present within 72 h of hospital admission that distinguish moderate from severe and fatal COVID-19 disease. Importantly, cellular and molecular states also distinguish participants with more severe disease that recover or stabilize within 28 days from those that progress to fatal outcomes (TG4 vs. TG5). Furthermore, our longitudinal design reveals that these biologic states display distinct temporal patterns associated with clinical outcomes. Characterizing host immune responses in relation to heterogeneity in disease course may inform clinical prognosis and opportunities for intervention.
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Affiliation(s)
- Joann Diray-Arce
- Clinical and Data Coordinating Center, Boston Children's Hospital, Boston, MA 02115, USA; Precision Vaccines Program, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
| | - Slim Fourati
- Emory School of Medicine, Atlanta, GA 30322, USA
| | | | - Ravi Patel
- University of California San Francisco, San Francisco, CA 94115, USA
| | - Cole Maguire
- The University of Texas at Austin, Austin, TX 78712, USA
| | - Ana C Chang
- Clinical and Data Coordinating Center, Boston Children's Hospital, Boston, MA 02115, USA
| | - Ravi Dandekar
- University of California San Francisco, San Francisco, CA 94115, USA
| | - Jingjing Qi
- Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Brian H Lee
- Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Patrick van Zalm
- Precision Vaccines Program, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA
| | - Andrew Schroeder
- University of California San Francisco, San Francisco, CA 94115, USA
| | - Ernie Chen
- Yale School of Medicine, New Haven, CT 06510, USA
| | | | | | | | - Alvin Kho
- Clinical and Data Coordinating Center, Boston Children's Hospital, Boston, MA 02115, USA
| | - Jing Chen
- Clinical and Data Coordinating Center, Boston Children's Hospital, Boston, MA 02115, USA; Precision Vaccines Program, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA
| | | | | | - Annmarie Hoch
- Clinical and Data Coordinating Center, Boston Children's Hospital, Boston, MA 02115, USA; Precision Vaccines Program, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA
| | - Carly E Milliren
- Clinical and Data Coordinating Center, Boston Children's Hospital, Boston, MA 02115, USA
| | | | | | - Charles B Cairns
- Drexel University, Tower Health Hospital, Philadelphia, PA 19104, USA
| | | | | | | | - Florian Krammer
- Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Lindsey Rosen
- National Institute of Allergy and Infectious Diseases, National Institute of Health, Bethesda, MD 20814, USA
| | | | - Harm van Bakel
- Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Michael Wilson
- University of California San Francisco, San Francisco, CA 94115, USA
| | - Jayant Rajan
- University of California San Francisco, San Francisco, CA 94115, USA
| | - Hanno Steen
- Precision Vaccines Program, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA
| | - Walter Eckalbar
- University of California San Francisco, San Francisco, CA 94115, USA
| | - Chris Cotsapas
- Yale School of Medicine, New Haven, CT 06510, USA; Broad Institute of MIT & Harvard, Cambridge, MA 02142, USA
| | | | - Ofer Levy
- Precision Vaccines Program, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT & Harvard, Cambridge, MA 02142, USA
| | - Matthew C Altman
- Benaroya Research Institute, University of Washington, Seattle, WA 98101, USA
| | - Holden Maecker
- Stanford University School of Medicine, Palo Alto, CA 94305, USA
| | | | - Elias K Haddad
- Drexel University, Tower Health Hospital, Philadelphia, PA 19104, USA
| | | | | | - Al Ozonoff
- Clinical and Data Coordinating Center, Boston Children's Hospital, Boston, MA 02115, USA; Precision Vaccines Program, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT & Harvard, Cambridge, MA 02142, USA
| | - Patrice M Becker
- National Institute of Allergy and Infectious Diseases, National Institute of Health, Bethesda, MD 20814, USA
| | - Alison D Augustine
- National Institute of Allergy and Infectious Diseases, National Institute of Health, Bethesda, MD 20814, USA
| | - Leying Guan
- Yale School of Public Health, New Haven, CT 06510, USA
| | - Bjoern Peters
- La Jolla Institute for Immunology, La Jolla, CA 92037, USA
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14
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Gjorgjieva T, Chaloemtoem A, Shahin T, Bayaraa O, Dieng MM, Alshaikh M, Abdalbaqi M, Del Monte J, Begum G, Leonor C, Manikandan V, Drou N, Arshad M, Arnoux M, Kumar N, Jabari A, Abdulle A, ElGhazali G, Ali R, Shaheen SY, Abdalla J, Piano F, Gunsalus KC, Daggag H, Al Nahdi H, Abuzeid H, Idaghdour Y. Systems genetics identifies miRNA-mediated regulation of host response in COVID-19. Hum Genomics 2023; 17:49. [PMID: 37303042 DOI: 10.1186/s40246-023-00494-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2023] [Accepted: 05/10/2023] [Indexed: 06/13/2023] Open
Abstract
BACKGROUND Individuals infected with SARS-CoV-2 vary greatly in their disease severity, ranging from asymptomatic infection to severe disease. The regulation of gene expression is an important mechanism in the host immune response and can modulate the outcome of the disease. miRNAs play important roles in post-transcriptional regulation with consequences on downstream molecular and cellular host immune response processes. The nature and magnitude of miRNA perturbations associated with blood phenotypes and intensive care unit (ICU) admission in COVID-19 are poorly understood. RESULTS We combined multi-omics profiling-genotyping, miRNA and RNA expression, measured at the time of hospital admission soon after the onset of COVID-19 symptoms-with phenotypes from electronic health records to understand how miRNA expression contributes to variation in disease severity in a diverse cohort of 259 unvaccinated patients in Abu Dhabi, United Arab Emirates. We analyzed 62 clinical variables and expression levels of 632 miRNAs measured at admission and identified 97 miRNAs associated with 8 blood phenotypes significantly associated with later ICU admission. Integrative miRNA-mRNA cross-correlation analysis identified multiple miRNA-mRNA-blood endophenotype associations and revealed the effect of miR-143-3p on neutrophil count mediated by the expression of its target gene BCL2. We report 168 significant cis-miRNA expression quantitative trait loci, 57 of which implicate miRNAs associated with either ICU admission or a blood endophenotype. CONCLUSIONS This systems genetics study has given rise to a genomic picture of the architecture of whole blood miRNAs in unvaccinated COVID-19 patients and pinpoints post-transcriptional regulation as a potential mechanism that impacts blood traits underlying COVID-19 severity. The results also highlight the impact of host genetic regulatory control of miRNA expression in early stages of COVID-19 disease.
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Affiliation(s)
- T Gjorgjieva
- Biology Program, Division of Science, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates.
- Public Health Research Center, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates.
| | - A Chaloemtoem
- Biology Program, Division of Science, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates
| | - T Shahin
- Biology Program, Division of Science, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates
| | - O Bayaraa
- Biology Program, Division of Science, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates
| | - M M Dieng
- Biology Program, Division of Science, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates
| | - M Alshaikh
- Public Health Research Center, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates
| | - M Abdalbaqi
- Public Health Research Center, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates
| | - J Del Monte
- Public Health Research Center, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates
| | - G Begum
- Public Health Research Center, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates
| | - C Leonor
- Biology Program, Division of Science, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates
| | - V Manikandan
- Biology Program, Division of Science, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates
| | - N Drou
- Center for Genomics and Systems Biology, NYU Abu Dhabi, Abu Dhabi, United Arab Emirates
| | - M Arshad
- Center for Genomics and Systems Biology, NYU Abu Dhabi, Abu Dhabi, United Arab Emirates
| | - M Arnoux
- Center for Genomics and Systems Biology, NYU Abu Dhabi, Abu Dhabi, United Arab Emirates
| | - N Kumar
- Seha (Abu Dhabi Health Services Company), Abu Dhabi, United Arab Emirates
| | - A Jabari
- Public Health Research Center, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates
| | - A Abdulle
- Public Health Research Center, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates
| | - G ElGhazali
- Sheikh Khalifa Medical City-Union 71 PureHealth, Abu Dhabi, United Arab Emirates
- Department of Medical Microbiology and Immunology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates
| | - R Ali
- Public Health Research Center, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates
| | - S Y Shaheen
- Department of Medical Microbiology and Immunology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates
| | - J Abdalla
- Department of Medical Microbiology and Immunology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates
| | - F Piano
- Biology Program, Division of Science, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates
- Public Health Research Center, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates
- Center for Genomics and Systems Biology, NYU Abu Dhabi, Abu Dhabi, United Arab Emirates
| | - K C Gunsalus
- Biology Program, Division of Science, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates
- Public Health Research Center, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates
- Center for Genomics and Systems Biology, NYU Abu Dhabi, Abu Dhabi, United Arab Emirates
| | - H Daggag
- Seha (Abu Dhabi Health Services Company), Abu Dhabi, United Arab Emirates
| | - H Al Nahdi
- Seha (Abu Dhabi Health Services Company), Abu Dhabi, United Arab Emirates
| | - H Abuzeid
- Seha (Abu Dhabi Health Services Company), Abu Dhabi, United Arab Emirates
| | - Y Idaghdour
- Biology Program, Division of Science, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates.
- Public Health Research Center, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates.
- Center for Genomics and Systems Biology, NYU Abu Dhabi, Abu Dhabi, United Arab Emirates.
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15
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Abou Hassan FF, Bou Hamdan M, Melhem NM. Clinical Characteristics and Serum Cytokines Profiling in Hospitalized COVID-19 Patients in Lebanon. J Immunol Res 2023; 2023:7258585. [PMID: 37228441 PMCID: PMC10205405 DOI: 10.1155/2023/7258585] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2022] [Revised: 04/13/2023] [Accepted: 04/27/2023] [Indexed: 05/27/2023] Open
Abstract
Since its emergence, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a public health threat worldwide. While the majority of patients recover in 3-4 weeks, complications in severely ill patients, including acute respiratory distress syndrome, cardiac injury, thrombosis, and sepsis, can lead to death. Several biomarkers, in addition to cytokine release syndrome (CRS), have been associated with severe and fatal outcomes in coronavirus disease 2019 (COVID-19) patients. The aim of this study is to assess clinical characteristics and cytokines profiles in hospitalized COVID-19 patients in Lebanon. A total of 51 hospitalized COVID-19 patients were recruited between February 2021 and May 2022. Clinical data and sera were collected at two time points: at hospital presentation (T0) and last collected results during hospitalization (T1). Our results showed that 49% of participants were >60 years with males accounting for the majority (72.5%). Hypertension, followed by diabetes and dyslipidemia, were the most frequent comorbid conditions among study participants accounting for 56.9% and 31.4%, respectively. Chronic obstructive pulmonary disease (COPD) was the only significantly different comorbid condition between intensive care unit (ICU) and non-ICU patients. Our results also showed that the median level of D-dimer was significantly elevated among patients in ICU and those who died compared to non-ICU patients and those who survived. Moreover, C-reactive protein (CRP) levels were significantly higher at T0 compared to T1 in ICU and non-ICU patients. The median level of IL-12p70 was significantly higher in patients >60 years compared to those ≤60 years (p = 0.0209). Our data are in agreement with previous reports suggesting the importance of IL-6, CRP, and IL-12p70 in the assessment of risk of severe disease and mortality.
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Affiliation(s)
- Farouk F. Abou Hassan
- Medical Laboratory Sciences Program, Division of Health Professions, Faculty of Health Sciences, American University of Beirut, Beirut, Lebanon
| | - Mirna Bou Hamdan
- Medical Laboratory Sciences Program, Division of Health Professions, Faculty of Health Sciences, American University of Beirut, Beirut, Lebanon
| | - Nada M. Melhem
- Medical Laboratory Sciences Program, Division of Health Professions, Faculty of Health Sciences, American University of Beirut, Beirut, Lebanon
- Center for Infectious Diseases Research, Faculty of Medicine, American University of Beirut, Beirut, Lebanon
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16
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Abstract
From the onset of the pandemic, evidence of cardiac involvement in acute COVID-19 abounded. Cardiac presentations ranged from arrhythmias to ischemia, myopericarditis/myocarditis, ventricular dysfunction to acute heart failure, and even cardiogenic shock. Elevated serum cardiac troponin levels were prevalent among hospitalized patients with COVID-19; the higher the magnitude of troponin elevation, the greater the COVID-19 illness severity and in-hospital death risk. Whether these consequences were due to direct SARS-CoV-2 infection of cardiac cells or secondary to inflammatory responses steered early cardiac autopsy studies. SARS-CoV-2 was reportedly detected in endothelial cells, cardiac myocytes, and within the extracellular space. However, findings were inconsistent and different methodologies had their limitations. Initial autopsy reports suggested that SARS-CoV-2 myocarditis was common, setting off studies to find and phenotype inflammatory infiltrates in the heart. Nonetheless, subsequent studies rarely detected myocarditis. Microthrombi, cardiomyocyte necrosis, and inflammatory infiltrates without cardiomyocyte damage were much more common. In vitro and ex vivo experimental platforms have assessed the cellular tropism of SARS-CoV-2 and elucidated mechanisms of viral entry into and replication within cardiac cells. Data point to pericytes as the primary target of SARS-CoV-2 in the heart. Infection of pericytes can account for the observed pericyte and endothelial cell death, innate immune response, and immunothrombosis commonly observed in COVID-19 hearts. These processes are bidirectional and synergistic, rendering a definitive order of events elusive. Single-cell/nucleus analyses of COVID-19 myocardial tissue and isolated cardiac cells have provided granular data about the cellular composition and cell type-specific transcriptomic signatures of COVID-19 and microthrombi-positive COVID-19 hearts. Still, much remains unknown and more in vivo studies are needed. This review seeks to provide an overview of the current understanding of COVID-19 cardiac pathophysiology. Cell type-specific mechanisms and the studies that provided such insights will be highlighted. Given the unprecedented pace of COVID-19 research, more mechanistic details are sure to emerge since the writing of this review. Importantly, our current knowledge offers significant clues about the cardiac pathophysiology of long COVID-19, the increased postrecovery risk of cardiac events, and thus, the future landscape of cardiovascular disease.
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Affiliation(s)
- Emily J Tsai
- Division of Cardiology, Columbia University Vagelos College of Physicians & Surgeons, New York, NY (E.J.T.)
| | - Daniela Cˇiháková
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD (D.C.)
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17
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Popovska Jovičić B, Raković I, Gavrilović J, Sekulić Marković S, Petrović S, Marković V, Pavković A, Čanović P, Radojević Marjanović R, Irić-Čupić V, Popović Dragonjić L, Milosavljević MZ. Vitamin D, Albumin, and D-Dimer as Significant Prognostic Markers in Early Hospitalization in Patients with COVID-19. J Clin Med 2023; 12:2825. [PMID: 37109161 PMCID: PMC10145116 DOI: 10.3390/jcm12082825] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2023] [Revised: 03/13/2023] [Accepted: 03/23/2023] [Indexed: 04/29/2023] Open
Abstract
SARS-CoV-2 continues to pose a major challenge to scientists and clinicians. We examined the significance of the serum concentrations of vitamin D, albumin, and D-dimer for the severity of the clinical picture and mortality in COVID-19. MATERIALS AND METHODS A total of 288 patients treated for COVID-19 infection participated in the research. The patients were treated in the period from May 2020 to January 2021. All patients were divided based on the need for oxygen therapy (Sat > 94%) into patients with mild or severe clinical pictures. The biochemical and radiographic parameters of the patients were analyzed. Appropriate statistical methods were used in the statistical analysis. RESULTS In patients with COVID-19 with confirmed severe clinical pictures, lower values of serum albumin (p < 0.0005) and vitamin D (p = 0.004) were recorded, as opposed to elevated values of D-dimer (p < 0.0005). Accordingly, the patients with fatal disease outcomes had lower levels of albumin (p < 0.0005) and vitamin D (p = 0.002), while their D-dimer (p < 0.0005) levels were elevated. An increase in the radiographic score, as a parameter for assessing the severity of the clinical picture, was accompanied by a decrease in serum albumin (p < 0.0005) and a simultaneous increase in D-dimer (p < 0.0005), without a change in the vitamin D concentration (p = 0.261). We also demonstrated the interrelations of the serum levels of vitamin D, albumin, and D-dimer in patients with COVID-19 as well as their significance as predictors of the outcome of the disease. CONCLUSION The significance of the predictive parameters in our study indicates the existence of an important combined role of vitamin D, albumin, and D-dimer in the early diagnosis of the most severe patients suffering from COVID-19. Reduced values of vitamin D and albumin, in combination with elevated values of D-dimer, can be timely indicators of the development of a severe clinical picture and death due to COVID-19.
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Affiliation(s)
- Biljana Popovska Jovičić
- Department of Infectious Diseases, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia
- Clinic for Infectious Diseases, University Clinical Center Kragujevac, Zmaj Jovina 30, 34000 Kragujevac, Serbia
| | - Ivana Raković
- Department of Infectious Diseases, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia
- Clinic for Infectious Diseases, University Clinical Center Kragujevac, Zmaj Jovina 30, 34000 Kragujevac, Serbia
| | - Jagoda Gavrilović
- Department of Infectious Diseases, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia
- Clinic for Infectious Diseases, University Clinical Center Kragujevac, Zmaj Jovina 30, 34000 Kragujevac, Serbia
| | - Sofija Sekulić Marković
- Department of Infectious Diseases, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia
- Clinic for Infectious Diseases, University Clinical Center Kragujevac, Zmaj Jovina 30, 34000 Kragujevac, Serbia
| | - Sara Petrović
- Department of Infectious Diseases, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia
- Clinic for Infectious Diseases, University Clinical Center Kragujevac, Zmaj Jovina 30, 34000 Kragujevac, Serbia
| | - Vladan Marković
- Department of Radiology, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia
- Department of Radiological Diagnostics, University Clinical Center Kragujevac, 34000 Kragujevac, Serbia
| | - Aleksandar Pavković
- Department of Radiological Diagnostics, University Clinical Center Kragujevac, 34000 Kragujevac, Serbia
| | - Predrag Čanović
- Department of Infectious Diseases, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia
- Clinic for Infectious Diseases, University Clinical Center Kragujevac, Zmaj Jovina 30, 34000 Kragujevac, Serbia
| | - Ružica Radojević Marjanović
- Clinic for Infectious Diseases, University Clinical Center Kragujevac, Zmaj Jovina 30, 34000 Kragujevac, Serbia
| | - Violeta Irić-Čupić
- Department of Internal Medicine, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia
- Clinic for Cardiology, University Clinical Center Kragujevac, 34000 Kragujevac, Serbia
| | - Lidija Popović Dragonjić
- University of Niš, Faculty of Medicine in Nis, Cathedra for Infectious Diseases and Epidemiology, Blvd. Dr Zorana Djindjica 81, 18000 Niš, Serbia
- Clinic for Infectology, University Clinical Center Niš, 18000 Niš, Serbia
| | - Miloš Z. Milosavljević
- Department of Pathology, University Clinical Center Kragujevac, 34000 Kragujevac, Serbia
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18
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Azizi BA, Munoz-Acuna R, Suleiman A, Ahrens E, Redaelli S, Tartler TM, Chen G, Jung B, Talmor D, Baedorf-Kassis EN, Schaefer MS. Mechanical power and 30-day mortality in mechanically ventilated, critically ill patients with and without Coronavirus Disease-2019: a hospital registry study. J Intensive Care 2023; 11:14. [PMID: 37024938 PMCID: PMC10077655 DOI: 10.1186/s40560-023-00662-7] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2023] [Accepted: 03/31/2023] [Indexed: 04/08/2023] Open
Abstract
BACKGROUND Previous studies linked a high intensity of ventilation, measured as mechanical power, to mortality in patients suffering from "classic" ARDS. By contrast, mechanically ventilated patients with a diagnosis of COVID-19 may present with intact pulmonary mechanics while undergoing mechanical ventilation for longer periods of time. We investigated whether an association between higher mechanical power and mortality is modified by a diagnosis of COVID-19. METHODS This retrospective study included critically ill, adult patients who were mechanically ventilated for at least 24 h between March 2020 and December 2021 at a tertiary healthcare facility in Boston, Massachusetts. The primary exposure was median mechanical power during the first 24 h of mechanical ventilation, calculated using a previously validated formula. The primary outcome was 30-day mortality. As co-primary analysis, we investigated whether a diagnosis of COVID-19 modified the primary association. We further investigated the association between mechanical power and days being alive and ventilator free and effect modification of this by a diagnosis of COVID-19. Multivariable logistic regression, effect modification and negative binomial regression analyses adjusted for baseline patient characteristics, severity of disease and in-hospital factors, were applied. RESULTS 1,737 mechanically ventilated patients were included, 411 (23.7%) suffered from COVID-19. 509 (29.3%) died within 30 days. The median mechanical power during the first 24 h of ventilation was 19.3 [14.6-24.0] J/min in patients with and 13.2 [10.2-18.0] J/min in patients without COVID-19. A higher mechanical power was associated with 30-day mortality (ORadj 1.26 per 1-SD, 7.1J/min increase; 95% CI 1.09-1.46; p = 0.002). Effect modification and interaction analysis did not support that this association was modified by a diagnosis of COVID-19 (95% CI, 0.81-1.38; p-for-interaction = 0.68). A higher mechanical power was associated with a lower number of days alive and ventilator free until day 28 (IRRadj 0.83 per 7.1 J/min increase; 95% CI 0.75-0.91; p < 0.001, adjusted risk difference - 2.7 days per 7.1J/min increase; 95% CI - 4.1 to - 1.3). CONCLUSION A higher mechanical power is associated with elevated 30-day mortality. While patients with COVID-19 received mechanical ventilation with higher mechanical power, this association was independent of a concomitant diagnosis of COVID-19.
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Affiliation(s)
- Basit A Azizi
- Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Brookline Ave 330, Boston, MA, USA
- Center for Anesthesia Research Excellence (CARE), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Ricardo Munoz-Acuna
- Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Brookline Ave 330, Boston, MA, USA
- Center for Anesthesia Research Excellence (CARE), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Aiman Suleiman
- Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Brookline Ave 330, Boston, MA, USA
- Center for Anesthesia Research Excellence (CARE), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Elena Ahrens
- Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Brookline Ave 330, Boston, MA, USA
- Center for Anesthesia Research Excellence (CARE), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Simone Redaelli
- Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Brookline Ave 330, Boston, MA, USA
- Center for Anesthesia Research Excellence (CARE), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Tim M Tartler
- Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Brookline Ave 330, Boston, MA, USA
- Center for Anesthesia Research Excellence (CARE), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Guanqing Chen
- Center for Anesthesia Research Excellence (CARE), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Boris Jung
- Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Brookline Ave 330, Boston, MA, USA
- Center for Anesthesia Research Excellence (CARE), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Daniel Talmor
- Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Brookline Ave 330, Boston, MA, USA
| | - Elias N Baedorf-Kassis
- Division of Pulmonary and Critical Care, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Maximilian S Schaefer
- Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Brookline Ave 330, Boston, MA, USA.
- Center for Anesthesia Research Excellence (CARE), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
- Department of Anesthesiology, Duesseldorf University Hospital, Duesseldorf, Germany.
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19
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AlGhawi FS, AlMudarra SS, Assiri AM. Mortality patterns among COVID-19 patients in two Saudi hospitals: Demographics, etiology, and treatment. Influenza Other Respir Viruses 2023; 17:e13127. [PMID: 36970568 PMCID: PMC10030359 DOI: 10.1111/irv.13127] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Revised: 02/26/2023] [Accepted: 03/02/2023] [Indexed: 03/24/2023] Open
Abstract
Background Saudi Arabia (SA) reported its first case of COVID-19 on 2 March 2020. Mortality varied nationwide; by April 14, 2020, Medina had 16% of SA's total COVID-19 cases and 40% of all COVID-19 deaths. A team of epidemiologists investigated to identify factors impacting survival. Methods We reviewed medical records from two hospitals: Hospital A in Medina and Hospital B in Dammam. All patients with a registered COVID-related death between March and May 1, 2020, were included. We collected data on demographics, chronic health conditions, clinical presentation, and treatment. We analyzed data using SPSS. Results We identified 76 cases: 38 cases from each hospital. More fatalities were among non-Saudis at Hospital A (89%) versus Hospital B (82%, p < 0.001). Hypertension prevalence was higher among cases at Hospital B (42%) versus Hospital A (21%) (p < 0.05). We found statistically significant differences (p < 0.05) in symptoms at initial presentation among cases at Hospital B versus Hospital A, including body temperature (38°C vs. 37°C), heart rate (104 bpm vs. 89 bpm), and regular breathing rhythms (61% vs. 55%). Fewer cases (50%) at Hospital A received heparin versus Hospital B (97%, p-value < 0.001). Conclusion Patients who died typically presented with more severe illnesses and were more likely to have underlying health conditions. Migrant workers may be at increased risk due to poorer baseline health and reluctance to seek care. This highlights the importance of cross-cultural outreach to prevent deaths. Health education efforts should be multilingual and accommodate all literacy levels.
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Affiliation(s)
| | - Sami S. AlMudarra
- Field Epidemiology Training ProgramMinistry of HealthRiyadhSaudi Arabia
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20
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Brechko A, Jiroutek MR, Jones K, Brenseke B, Maharty DC, Cappola J, Holly SP. Retrospective Study of Thrombosis in Hospitalized Patients with COVID-19 in Rural North Carolina. N C Med J 2023; 84:127-133. [PMID: 39302334 DOI: 10.18043/001c.73024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/22/2024]
Abstract
Background Some patients with COVID-19 develop life-threatening thrombotic complications including myocardial infarction, deep vein thrombosis, pulmonary embolism, disseminated intravascular coagulation, and ischemic stroke. These inflammatory and hypercoagulable states have been well documented in patient cohorts from metropolitan areas, but not in more rural populations, nor has a data-driven treatment plan been developed for thrombotic COVID-19 patients. Methods We undertook a retrospective case-control study of COVID-19-positive patients to analyze the impact of thrombosis on various clinical endpoints including terminal diagnosis and disease severity. Prevalence and impact of thrombosis were determined using medical records from 2237 COVID-19-positive patients hospitalized in Cumberland County, North Carolina. Odds ratios for terminal diagnosis, death, ICU admission, and ventilation were calculated based on thrombosis status, D-dimer level, or type of antithrombotic treatment. Results Terminal diagnosis [OR 1.81; 95% CI (1.10, 2.98)], ICU admission [2.25; (1.33, 3.81)], and ventilation [2.46; (1.45, 4.18)] were all more likely in thrombotic patients (N = 97) compared to nonthrombotic patients (N = 2140) after adjusting for age. D-dimer levels were associated with death overall, but not among thrombotic patients. Treatments that combined antiplatelet and anticoagulant drugs appeared to be more efficacious than anticoagulants alone in preventing death and severe disease. Limitations Patient medical history prior to hospitalization was not evaluated. Conclusion In this cohort, those with thrombosis are at increased risk for adverse outcomes including death and severe disease. Antithrombotic therapy that includes antiplatelet drugs provides improved outcomes. Higher-powered prospective trials will be necessary to confirm any potential merits of antiplatelet therapy.
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Affiliation(s)
| | | | - Kyla Jones
- Jerry M. Wallace School of Osteopathic Medicine, Campbell University
| | - Bonnie Brenseke
- Jerry M. Wallace School of Osteopathic Medicine, Campbell University
| | - Donald C Maharty
- Jerry M. Wallace School of Osteopathic Medicine, Campbell University
- Cape Fear Valley Medical Center
| | - James Cappola
- Jerry M. Wallace School of Osteopathic Medicine, Campbell University
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21
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Anton MC, Shanthi B, Vasudevan E. Study to Determine a Prognostic Cutoff Values of the Coagulation Analyte D-dimer for ICU Admission among COVID-19 Patients. Indian J Crit Care Med 2023; 27:135-138. [PMID: 36865519 PMCID: PMC9973051 DOI: 10.5005/jp-journals-10071-24395] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2022] [Accepted: 10/11/2022] [Indexed: 02/04/2023] Open
Abstract
Introduction The measured D-dimer levels in coronavirus disease-2019 (COVID-19) patients have no specific cutoff to find the progression of coagulopathy and severity. Aim This study aimed to determine prognostic cutoff values of D-dimer for intensive care unit (ICU) admission among COVID-19 patients. Materials and methods This cross-sectional study was conducted in Sree Balaji Medical College and Hospital, Chennai, during a period of 6 months. This study included 460 COVID-19-positive individuals. Results The mean age was 52.2 ± 12.53 years. Patients with mild illness have D-dimer value 461.8 ± 221, whereas moderate and severe COVID illness patients have D-dimer values of 1915.2 ± 699.9 and 7937.6 ± 2045.2, respectively. D-dimer cutoff value of 1036.9 is shown to be a prognostic cutoff value for COVID-19 patients admitted in the ICU with 99% sensitivity and 17% specificity. The area under curve (AUC) was considered excellent (AUC = 0.827, 95% Cl: 0.78-0.86, p-value < 0.0001) indicative of high sensitivity. Conclusion The D-dimer value of 1036.9 ng/mL was found to be the optimum cutoff for the patients to predict the severity of the COVID-19-positive patients admitted in the ICU. How to cite this article Anton MC, Shanthi B, Vasudevan E. Study to Determine a Prognostic Cutoff Values of the Coagulation Analyte D-dimer for ICU Admission among COVID-19 Patients. Indian J Crit Care Med 2023;27(2):135-138.
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Affiliation(s)
- Mary Chandrika Anton
- Department of Biochemistry, Bhaarath Medical College and Hospital and Bharath Institute of Higher Education and Research, Chennai, Tamil Nadu, India,Mary Chandrika Anton, Department of Biochemistry, Bhaarath Medical College and Hospital and Bharath Institute of Higher Education and Research, Chennai, Tamil Nadu, India, Phone: +91 04422415603, e-mail:
| | - B Shanthi
- Department of Biochemistry, Sree Balaji Medical College and Hospital, Chennai, Tamil Nadu, India
| | - E Vasudevan
- Department of Biochemistry, Sree Balaji Medical College and Hospital, Chennai, Tamil Nadu, India
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22
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Hojker M, Tršan J, Tršan U, Gale A, Jerman A, Košuta D. Predictive value of inflammatory and coagulation biomarkers for venous thromboembolism in Covid-19 patients. Clin Hemorheol Microcirc 2023; 83:387-395. [PMID: 36683498 DOI: 10.3233/ch-221664] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
BACKGROUND The predictive value of coagulation markers for venous thromboembolism (VTE) in Covid-19 patients has been investigated with conflicting results. OBJECTIVE Our aim was to investigate the correlation between biomarkers and VTE and the predictive value of D-dimer for VTE in hospitalized Covid-19 patients. METHODS Complete blood count, inflammatory and coagulation biomarkers at admission were collected. VTE was defined as diagnosed pulmonary embolism or deep vein thrombosis. Events were defined as in-hospital death or ICU admission. Predictors of VTE were identified with Pearson prediction models. A ROC curve was constructed to assess the predictive value of D-dimer. RESULTS 1651 participants were included, 111 VTE were identified. Events incidence was higher in the VTE group (49.5% vs 28.2%, p < 0.001). Neutrophil-lymphocyte ratio (NLR, 0.001; 95% CI 0.000-0.002; p 0.019) and D-dimer (0.00005; 95% CI 0.00002-0.00008; p < 0.001), Geneva score (0.026; 95% CI 0.012-0.040; p < 0.001) and Wells score (0.047; 95% CI 0.033-0.061; p < 0.001) were associated with VTE. D-dimer had a goor predictive value for VTE (ROC area 0.85, 95% CI 0.816-0.893), with an optimal cut-off value of 2677μg/L (Youden index of 0,602). CONCLUSIONS Among coagulation biomarkers D-dimer had the best predictive value for VTE, but higher cut-off values should be used in Covid-19.
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Affiliation(s)
- Marta Hojker
- University Medical Centre Ljubljana, Department of Orthopaedic Surgery, Ljubljana, Slovenia.,University of Ljubljana, Faculty of Medicine, Ljubljana, Slovenia
| | - Jure Tršan
- University of Ljubljana, Faculty of Medicine, Ljubljana, Slovenia.,University Medical Centre Ljubljana, Department of Vascular Diseases, Ljubljana, Slovenia
| | - Uroš Tršan
- University of Ljubljana, Faculty of Medicine, Ljubljana, Slovenia
| | - Ana Gale
- University Medical Centre Ljubljana, Department of Dermatovenereology, Ljubljana, Slovenia
| | - Alexander Jerman
- University Medical Centre Ljubljana, Department of Nephrology, Ljubljana, Slovenia
| | - Daniel Košuta
- University of Ljubljana, Faculty of Medicine, Ljubljana, Slovenia.,University Medical Centre Ljubljana, Department of Vascular Diseases, Ljubljana, Slovenia
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23
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Correlation of Patient Profiles and Biomarkers with Outcomes in Covid-19 Icu Patients: A Retrospective Analysis. Rom J Anaesth Intensive Care 2022; 28:71-79. [PMID: 36844114 PMCID: PMC9949024 DOI: 10.2478/rjaic-2021-0012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/28/2023] Open
Abstract
Background COVID-19 is a novel disease with a highly variable and unpredictable clinical course. Various clinicodemographic factors and numerous biomarkers have been identified in studies from the West and marked as possible predictors of severe illness and mortality which may be used to triage patients for early aggressive care. This triaging becomes even more significant in resource-limited critical care settings of the Indian subcontinent. Methods This retrospective observational study recruited 99 cases of COVID-19 admitted to intensive care from 1 May to 1 August 2020. Demographic, clinical and baseline laboratory data were collected and analysed for association with clinical outcomes, including survival and need for mechanical ventilatory support. Results Male gender (p=0.044) and diabetes mellitus (p=0.042) were associated with increased mortality. Binomial logistic regression analysis revealed Interleukin-6 (IL6) (p=0.024), D-dimer (p=0.025) and CRP (p<0.001) as significant predictors of need of ventilatory support and IL6 (p=0.036), CRP (p=0.041), D-dimer (p=0.006) and PaO2FiO2 ratio (p=0.019) as significant predictors of mortality. CRP >40 mg/L predicted mortality with sensitivity of 93.3% and specificity of 88.9% (AUC 0.933) and IL6> 32.5 pg/ml with a sensitivity of 82.2% and specificity of 70.4% (AUC 0.821). Conclusion Our results suggest that a baseline CRP >40 mg/L, IL6 >32.5 pg/ml or D-dimer >810 ng/ml are early accurate predictors of severe illness and adverse outcomes and may be used to triage patients for early intensive care.
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24
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Tortolini C, Gigli V, Angeloni A, Galantini L, Tasca F, Antiochia R. Disposable Voltammetric Immunosensor for D-Dimer Detection as Early Biomarker of Thromboembolic Disease and of COVID-19 Prognosis. BIOSENSORS 2022; 13:bios13010043. [PMID: 36671877 PMCID: PMC9855840 DOI: 10.3390/bios13010043] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/27/2022] [Revised: 12/16/2022] [Accepted: 12/24/2022] [Indexed: 06/12/2023]
Abstract
In this work, we report on the development of a simple electrochemical immunosensor for the detection of D-dimer protein in human plasma samples. The immunosensor is built by a simple drop-casting procedure of chitosan nanoparticles (CSNPs) as biocompatible support, Protein A (PrA), to facilitate the proper orientation of the antibody sites to epitopes as a capture biomolecule, and the D-dimer antibody onto a carboxyl functionalized multi-walled carbon nanotubes screen printed electrode (MWCNTs-SPE). The CSNPs have been morphologically characterized by Scanning Electron Microscopy (SEM) and Dynamic Light Scattering (DLS) techniques. Successively, the electrochemical properties of the screen-printed working electrode after each modification step have been characterized by differential pulse voltammetry (DPV) and electrochemical impedance spectroscopy (EIS). The resulting MWCNTs-CSNPs-PrA-D-dimer Ab immunosensor displays an optimal and promising platform for antibody immobilization and specific D-dimer detection. DPV has been used to investigate the antigen/antibody interaction at different D-dimer concentrations. The proposed voltammetric immunosensor allowed a linear range from 2 to 500 μg L-1 with a LOD of 0.6 μg L-1 and a sensitivity of 1.3 μA L μg-1 cm-2. Good stability and a fast response time (5 s) have been reported. Lastly, the performance of the voltammetric immunosensor has been tested in human plasma samples, showing satisfactory results, thus attesting to the promising feasibility of the proposed platform for detecting D-dimer in physiological samples.
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Affiliation(s)
- Cristina Tortolini
- Department of Experimental Medicine, Sapienza University of Rome, V.le Regina Elena 324, 00166 Rome, Italy
| | - Valeria Gigli
- Department of Experimental Medicine, Sapienza University of Rome, V.le Regina Elena 324, 00166 Rome, Italy
| | - Antonio Angeloni
- Department of Experimental Medicine, Sapienza University of Rome, V.le Regina Elena 324, 00166 Rome, Italy
| | - Luciano Galantini
- Department of Chemistry, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy
| | - Federico Tasca
- Departamento de Química de los Materiales, Facultad de Química y Biología, Universidad de Santiago de Chile, Casilla 40, Correo 33, Sucursal Matucana, Santiago 9170022, Chile
| | - Riccarda Antiochia
- Department of Chemistry and Drug Technologies, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy
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25
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Meisinger C, Kirchberger I, Warm TD, Hyhlik-Dürr A, Goßlau Y, Linseisen J. Elevated Plasma D-Dimer Concentrations in Adults after an Outpatient-Treated COVID-19 Infection. Viruses 2022; 14:2441. [PMID: 36366539 PMCID: PMC9699049 DOI: 10.3390/v14112441] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Revised: 10/25/2022] [Accepted: 10/31/2022] [Indexed: 11/06/2022] Open
Abstract
Elevated D-dimer plasma concentrations are common in hospitalized COVID-19 patients and are often associated with a worse prognosis, but it is not yet clear whether this also applies to outpatient cases. The present cross-sectional study evaluated D-dimer levels and their association with clinical parameters and inflammation biomarkers after a COVID-19 disease in individuals treated as outpatients. The study included 411 individuals (43.3% men) with an average age of 46.8 years (SD 15.2). Study participants who had acute COVID-19 disease at a median of 235 days (120; 323) ago were examined at the University Hospital Augsburg, Southern Germany, between 11/2020 and 05/2021. Plasma D-dimers were measured by a particle-enhanced immunoturbidimetric assay. Sixty-one subjects (15%) showed increased D-dimer concentrations (≥500 µg/L). Study participants with elevated D-dimer levels in comparison to subjects with levels in the reference range were significantly older, and more frequently reported a history of cardiovascular disease, hypertension, venous thromboembolism, and chronic venous insufficiency. In multivariable logistic regression analysis, CRP levels (OR 5.58 per mg/dL, 95% CI 1.77-17.60) and white blood cell count (OR 1.48 per nL, 95% CI 1.19-1.83) were significantly related to elevated D-dimers even after adjustment for multiple testing. However, acute or persistent symptoms were not significantly associated with increased D-dimers. Elevated D-dimer levels months after an acute COVID-19 disease seems to be associated with markers of inflammation. Further studies are needed to investigate the underlying pathophysiological mechanisms and consequences of prolonged D-dimer elevation in these patients.
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Affiliation(s)
- Christa Meisinger
- Epidemiology, Faculty of Medicine, University Hospital of Augsburg, University of Augsburg, 86156 Augsburg, Germany
| | - Inge Kirchberger
- Epidemiology, Faculty of Medicine, University Hospital of Augsburg, University of Augsburg, 86156 Augsburg, Germany
- Institute for Medical Information Processing, Biometry and Epidemiology-IBE, LMU Munich, 80539 Munich, Germany
| | - Tobias D. Warm
- Vascular Surgery, Faculty of Medicine, University of Augsburg, 86159 Augsburg, Germany
| | - Alexander Hyhlik-Dürr
- Vascular Surgery, Faculty of Medicine, University of Augsburg, 86159 Augsburg, Germany
| | - Yvonne Goßlau
- Vascular Surgery, Faculty of Medicine, University of Augsburg, 86159 Augsburg, Germany
| | - Jakob Linseisen
- Epidemiology, Faculty of Medicine, University Hospital of Augsburg, University of Augsburg, 86156 Augsburg, Germany
- Institute for Medical Information Processing, Biometry and Epidemiology-IBE, LMU Munich, 80539 Munich, Germany
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Baltan E, Serin E, Avci BY, Akilli IK, Çinar AS. The relationship between plasminogen activator inhibitor-1 levels and the course of disease in COVID-19 patients. TURKISH JOURNAL OF BIOCHEMISTRY 2022; 47:672-679. [DOI: 10.1515/tjb-2022-0044] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
Abstract
Objectives
Studies have shown that fibrinolysis activity is insufficient in COVID-19 patients. Plasminogen activator inhibitor-1 (PAI-1) is an important antifibrinolytic molecule that plays a key role in the fibrinolytic system. In our study; we aimed to evaluate serum PAI-1 and other biochemical parameters of COVID-19 patients in terms of disease course and mortality.
Methods
A total of 40 COVID-19 patients were hospitalized in the service and intensive care unit (ICU) of our hospital from October to December 2020 and 20 healthy volunteers were included in our study. The patients were grouped as those who transferred to the ICU from the service and transferred to service from the ICU. The first and second values of the same patients in both the service and the ICU were analyzed by SPSS.
Results
The PAI-1 levels of the patients in the ICU were significantly higher than the levels of the same patients in the service and the healthy control group (p<0.001). IL-6, ferritin, and D-dimer levels in the ICU of the same patients were significantly higher than the levels of service and healthy control group (p<0.001). A positive correlation was found between initial serum PAI-1 and D-dimer levels in patients hospitalized in the service (p=0.039) and initial serum ferritin and IL-6 levels in the ICU (p=0.031).
Conclusions
In our study, we found that PAI-1 levels increased significantly with the increase in mortality in COVID-19 patients.
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Affiliation(s)
- Ecem Baltan
- Medical Biochemistry , Istanbul Şişli Hamidiye Etfal Training and Research Hospital , Sisli , Turkey
| | - Erdinç Serin
- Medical Biochemistry , Istanbul Şişli Hamidiye Etfal Training and Research Hospital , Sisli , Turkey
| | | | - Işil Kibar Akilli
- Department of Chest Diseases , Istanbul Şişli Hamidiye Etfal Training and Research Hospital , Sisli , Turkey
| | - Ayşe Sürhan Çinar
- Deparment of Anesthesiology and Reanimation , Istanbul Şişli Hamidiye Etfal Training and Research Hospital , Sisli , Turkey
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Pulmonary Involvement in SARS-CoV-2 Infection Estimates Myocardial Injury Risk. Medicina (B Aires) 2022; 58:medicina58101436. [PMID: 36295594 PMCID: PMC9610985 DOI: 10.3390/medicina58101436] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2022] [Revised: 10/06/2022] [Accepted: 10/08/2022] [Indexed: 11/21/2022] Open
Abstract
Background and Objectives: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection represents a pathology with primary pulmonary involvement and multisystemic impact, including cardiovascular injuries. The present study aimed to assess the value of clinical, biochemical, and imaging factors in COVID-19 patients in determining the severity of myocardial involvement, and to create a model that can be used toevaluate myocardial injury risk based on clinical, biochemical and imaging factors. Materials and Methods: We performed an observational cohort study on 150 consecutive patients, evaluating their age, sex, hospitalization period, peripheral oxygen saturation (SpO2) in ambient air, systolic and diastolic blood pressure, heart rate, respiratory rate, biochemical markers of cardiac dysfunction (TnI, and NT-proBNP), inflammatory markers (C reactive protein (CRP), fibrinogen, serum ferritin, interleukin-6 (IL-6), tumor necrosis factor alpha (TNFα)), D-dimers, lactate dehydrogenase (LDH), myoglobin and radio-imaging parameters. All patients underwent computerized tomography chest scan in the first two days following admission. Results: We observed elevated heart and respiratory rates, higher systolic blood pressure, and a lower diastolic blood pressure in the patients with cardiac injury; significant differences between groups were registered in TnI, NT-proBNP, LDH, CRP, and D-dimers. For the radiological parameters, we found proportional correlations with the myocardial injury for the severity of lung disease, number of pulmonary segments with alveolar consolidation, number of pulmonary lobes with pneumonia, crazy paving pattern, type of lung involvement, the extent of fibroatelectatic lesions and the mediastinal adenopathies. Conclusions: Myocardial injury occurred in 12% of patients in the study group. Ground glass opacities, interstitial interlobular septal thickening (crazy paving pattern), fibroatelectasic lesions and alveolar consolidations on CT scan were correlated with myocardial injury. Routine lung sectional imaging along with non-specific biomarkers (LDH, D-dimers, and CRP) can be further valuable in the characterization of the disease burden, thus impacting patient care.
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Xing Y, Yang W, Jin Y, Liu Y. Neutrophil count multiplied by D-dimer combined with pneumonia may better predict short-term outcomes in patients with acute ischemic stroke. PLoS One 2022; 17:e0275350. [PMID: 36206250 PMCID: PMC9543623 DOI: 10.1371/journal.pone.0275350] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2022] [Accepted: 09/14/2022] [Indexed: 11/06/2022] Open
Abstract
Objective To investigate the predictive value of neutrophil, D-dimer and diseases associated with stroke for short-term outcomes of acute ischemic stroke (AIS). Methods By collecting the subitems of laboratory data especially routine blood and coagulation test in AIS patients, and recording their clinical status, the correlation, regression and predictive value of each subitem with the short-term outcomes of AIS were analyzed. The predict model was constructed. Results The neutrophil count multiplied by D-dimer (NDM) had the best predictive value among the subitems, and the area under the receiver operating characteristic (ROC) curve reached 0.804. When clinical information was not considered, the Youden index of NDM was calculated to be 0.48, corresponding to an NDM value of 7.78, a diagnostic sensitivity of 0.79, specificity of 0.69, negative predictive value of 96%. NDM were divided into 5 quintiles, the five grade of NDM (quintile) were < = 1.82, 1.83–2.41, 2.42–3.27, 3.28–4.49, 4.95+, respectively. The multivariate regression analysis was conducted between NDM (quintile), Babinski+, pneumonia, cardiac disease and poor outcomes of AIS. Compared with the first grade of NDM (quintile), the second grade of NDM (quintile) was not significant, but the third grade of NDM (quintile) showed 7.061 times, the fourth grade of NDM (quintile) showed 11.776 times, the fifth grade of NDM (quintile) showed 23.394 times in short-term poor outcomes occurrence. Babinski sign + showed 1.512 times, pneumonia showed 2.995 times, cardiac disease showed 1.936 times in short-term poor outcomes occurrence compared with those negative patients. Conclusions NDM combined with pneumonia may better predict short-term outcomes in patients with AIS. Early prevention, regular examination and timely intervention should be emphasized for patients, which may reduce the risk of short-term poor outcomes.
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Affiliation(s)
- Yinting Xing
- Department of Clinical Laboratory, The Second Affiliated Hospital of Harbin Medical University, Harbin City, Heilongjiang Province, China
- Department of Clinical Laboratory, The First Affiliated Hospital of Harbin Medical University, Harbin City, Heilongjiang Province, China
- * E-mail: (YX); (YL)
| | - Wei Yang
- Department of Clinical Laboratory, The Second Affiliated Hospital of Harbin Medical University, Harbin City, Heilongjiang Province, China
- Department of Clinical Laboratory, The First Affiliated Hospital of Harbin Medical University, Harbin City, Heilongjiang Province, China
| | - Yingyu Jin
- Department of Clinical Laboratory, The First Affiliated Hospital of Harbin Medical University, Harbin City, Heilongjiang Province, China
| | - Yanhong Liu
- Department of Clinical Laboratory, The Second Affiliated Hospital of Harbin Medical University, Harbin City, Heilongjiang Province, China
- * E-mail: (YX); (YL)
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Grumet M, Sherman J, Dorf BS. Efficacy of MSC in Patients with Severe COVID-19: Analysis of the Literature and a Case Study. Stem Cells Transl Med 2022; 11:1103-1112. [PMID: 36181766 PMCID: PMC9672850 DOI: 10.1093/stcltm/szac067] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Accepted: 07/23/2022] [Indexed: 12/12/2022] Open
Abstract
Patients with severe COVID-19 experience cytokine storm, an uncontrolled upregulation of pro-inflammatory cytokines, which if unresolved leads to acute respiratory distress syndrome (ARDS), organ damage, and death. Treatments with mesenchymal stromal cells (MSC) [Viswanathan S, Shi Y, Galipeau J, et al. Mesenchymal stem versus stromal cells: International Society for Cell & Gene Therapy Mesenchymal Stromal Cell committee position statement on nomenclature. Cytotherapy. 2019;21:1019-1024] appear to be effective in reducing morbidity and mortality. MSC respond to pro-inflammatory cytokines by releasing anti-inflammatory factors and mobilizing immune cells. We analyzed 82 COVID-19 clinical trials registered at ClinicalTrials.gov to determine MSC dosing, routes of administration, and outcome measures. Nearly all trials described the use of intravenous delivery with most doses ranging between 50 and 125 million MSC/treatment, which overlaps with a minimal effective dose range that we described previously. We also searched the literature to analyze clinical trial reports that used MSC to treat COVID-19. MSC were found to improve survival and oxygenation, increase discharge from intensive care units and hospitals, and reduce levels of pro-inflammatory markers. We report on a 91-year-old man with severe COVID-19 who responded rapidly to MSC treatment with transient reductions in several pro-inflammatory markers and delayed improvement in oxygenation. The results suggest that frequent monitoring of pro-inflammatory markers for severe COVID-19 will provide improved treatment guidelines by determining relationships between cytokine storms and ARDS. We propose that markers for cytokine storm are leading indicators for ARDS and that measurement of cytokines will indicate earlier treatment with MSC than is performed now for ARDS in severe COVID-19.
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Affiliation(s)
- Martin Grumet
- W. M. Keck Center for Collaborative Neuroscience, Rutgers Stem Cell Research Center, Department of Cell Biology & Neuroscience, Rutgers University, Piscataway, NJ, USA
| | - Jason Sherman
- W. M. Keck Center for Collaborative Neuroscience, Rutgers Stem Cell Research Center, Department of Cell Biology & Neuroscience, Rutgers University, Piscataway, NJ, USA
| | - Barry S Dorf
- W. M. Keck Center for Collaborative Neuroscience, Rutgers Stem Cell Research Center, Department of Cell Biology & Neuroscience, Rutgers University, Piscataway, NJ, USA.,Department of Medicine, North Shore University Hospital, 300 Community Dr, Manhasset, NY, USA
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Chen J, Wang Y, Wang J, Chen L, Luo Q, Wang B, He X, Li X, Zuo H, Zuo P, Yang X. Coronavirus disease 2019 death prediction by electrocardiographic abnormalities and elevated D-dimer levels. Front Cardiovasc Med 2022; 9:948347. [PMID: 36247440 PMCID: PMC9554271 DOI: 10.3389/fcvm.2022.948347] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2022] [Accepted: 07/12/2022] [Indexed: 12/15/2022] Open
Abstract
Background Electrocardiography (ECG) plays a very important role in various cardiovascular diseases and elevated D-dimer in serum associated with thrombosis. In patients with coronavirus disease 2019 (COVID-19), immense pieces of evidence showed that ECG abnormalities or elevated D-dimer in serum occurred frequently. However, it remains unclear whether ECG abnormalities combined with elevated D-dimer could be a new risk predictor in patients with COVID-19. Methods and results This retrospective cohort study enrolled 416 patients with COVID-19 at Wuhan Tongji Hospital from 1 February to 20 March 2020. ECG manifestations, D-dimer levels, and in-hospital deaths were recorded for all patients. Logistic regression analysis was performed to examine the association between ECG manifestations and in-hospital mortality in patients with elevated D-dimer levels. In patients hospitalized for COVID-19, ST-T abnormalities (34.3%) were the most frequent ECG manifestations, whereas sinus tachycardia (ST) (13.3%) and atrial arrhythmias with rapid rhythms (8.5%) were the two most common cardiac arrhythmias. Compared to severely ill patients with COVID-19, ST-T abnormalities, ST and atrial arrhythmias (p<0.001) with rapid rhythms, D-dimer levels, and in-hospital deaths were significantly more frequent in critically ill patients with COVID-19. Moreover, elevated D-dimer levels were observed in all the patients who died. In the subgroup of 303 patients with elevated serum D-dimer levels, the patient's age, the incidence of ST-T abnormalities, ST, atrial fibrillation (AF), and atrial premature beat were significantly higher than those in the non-elevated D-dimer subgroup. Multivariate logistic regression analysis further revealed that ST and AF were risk factors for in-hospital mortality in COVID-19 patients with elevated D-dimer levels. Conclusions ECG abnormalities and elevated D-dimer levels were associated with a higher risk of critical illness and death in patients hospitalized for COVID-19. ECG abnormalities, including ST and AF, combined with elevated D-dimer levels, can be used to predict death in COVID-19.
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Affiliation(s)
- Jing Chen
- Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yina Wang
- Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jingyi Wang
- Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Lie Chen
- Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Qiushi Luo
- Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Bei Wang
- Department of Rheumatology and Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xingwei He
- Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xuefei Li
- Wuhan National High Magnetic Field Center, Huazhong University of Science & Technology, Wuhan, China
| | - Huakun Zuo
- Wuhan National High Magnetic Field Center, Huazhong University of Science & Technology, Wuhan, China
| | - Ping Zuo
- Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xiaoyun Yang
- Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Abbasher Hussien Mohamed Ahmed K, Hasabo EA, Haroun MS, Mah. Fadelallah Eljack M, Salih EH, Altayeb YFO, Nour AB, Abdallah AM, Osman WAM, Yousif MYE. Clinical characteristics, complications, and predictors of outcome of hospitalized adult Sudanese patients with COVID-19 and malaria coinfection in Sudan: A multicenter retrospective cross-sectional study. J Med Virol 2022; 94:3685-3697. [PMID: 35415939 PMCID: PMC9088527 DOI: 10.1002/jmv.27771] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2022] [Accepted: 04/10/2022] [Indexed: 01/08/2023]
Abstract
Malaria and coronavirus disease 2019 (COVID-19) share several characteristics that could lead to cross-infection, particularly in malaria-endemic areas. Early COVID-19 symptoms might be misdiagnosed for malaria in clinical settings. Also, both diseases can cause fatal complications. So, laboratory testing for both diseases was recommended by the World Health Organization. To study the clinical characteristics and outcomes of Adult Sudanese patients with COVID-19 and malaria coinfection. This retrospective cross-sectional study was conducted from January 2021 to October 2021 in Wad Medani. Total coverage of all Sudanese patients above 18 years old with a confirmed diagnosis of coinfection with COVID-19 and malaria was included, and data were collected using a data collection sheet. Data were analyzed using R software version 4.0.2. Data were described and presented as mean, standard deviation, and number (percentage). To find associated factors with in-hospital outcome, χ2 test, fisher exact test, and independent t test or Wilcoxon rank-sum test were used. In this study, 156 participants were diagnosed with COVID-19 and malaria coinfection. Most of them were between 60 and 70 years (30.8%), the majority were males (59%). Shortness of breath (76.3%) and acute respiratory distress syndrome (35.3%) were the most common symptom and complications among coinfected patients, respectively. Ground glass opacity (n = 47/49, 95.9%) is the most common result for computed tomography scan. Atrial fibrillation was the most common abnormal electrocardiogram finding (n = 6/62, 9.7%). Overall mortality among all participants was (63/156, 40.4%). High mortality rate was found among the coinfected patients. More attention is needed towards fighting COVID-19 and malaria coinfection. There may be a link between malaria and COVID-19.
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Bozkurt B, Das SR, Addison D, Gupta A, Jneid H, Khan SS, Koromia GA, Kulkarni PA, LaPoint K, Lewis EF, Michos ED, Peterson PN, Turagam MK, Wang TY, Yancy CW. 2022 AHA/ACC Key Data Elements and Definitions for Cardiovascular and Noncardiovascular Complications of COVID-19: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Data Standards. J Am Coll Cardiol 2022; 80:388-465. [PMID: 35753858 PMCID: PMC9222652 DOI: 10.1016/j.jacc.2022.03.355] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Ibrahim Abdullah Mahmood, Khalid Ahmed Mahmood, Nahidh Kamel Alwan. Predictive value of hematological and inflammatory markers for severity of COVID-19. Biomedicine (Taipei) 2022. [DOI: 10.51248/.v42i3.1619] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Introduction and Aim: Coronavirus disease 2019 (COVID–19) can cause damage to a wide variety of organs throughout the body, with the lung being its primary focus of attack. The identification of prognostic indicators in COVID-19 can be of assistance in the management of the disease, in instances that are critical or severe. The purpose of this study was to investigate the hematological and inflammatory indicators in COVID-19 patients who were hospitalized and determine how closely those markers are associated with the severity of the condition.
Materials and Methods: In this cross-sectional prospective analysis, there were a total of 200 patients diagnosed with COVID-19. The demographic information and comorbidities of the patients were gathered through direct questioning. The indicators of the complete blood count were recorded for every patient. In addition, tests were performed on D-dimer, ferritin, erythrocyte sedimentation rate (ESR), lactate dehydrogenase (LDH), and C reactive protein (CRP). Systemic immune inflammation index (SII) was calculated. The association of demographic and laboratory parameters with patient’s outcome evaluated.
Results: After a 30-day follow-up, 32 patients (16%) out of 200 required ICU hospitalization, with eight of them (4%) dying. Each of the following od diabetes (OR=4.2; 95 % CI= 1.8-2291, p=0.021), hypertension (OR=3.1, 95 % CI=1.21-19.11, p=0.033), D-dimmer (OR=3.22, 95 % CI=1.43-9.12, p=0.037), ferritin (OR=2.18, 95 % CI=1.4-7.22, p=0.027), NLR (OR=3.26, 95% CI=1.5-7.18, p= 0.023), LDH (OR= 6.23, 95% CI=1.77-22.9, p=0.034), and CRP (OR=4.56, 95% CI=1.32-28.85, p=0.007), were independent risk factors for severity of COVID-19.
Conclusion: The comorbidities diabetes and hypertension, as well as the levels of D-dimer, serum ferritin, NLR, LDH, and CRP, could be utilized to predict COVID-19 severity and its outcome.
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Bozkurt B, Das SR, Addison D, Gupta A, Jneid H, Khan SS, Koromia GA, Kulkarni PA, LaPoint K, Lewis EF, Michos ED, Peterson PN, Turagam MK, Wang TY, Yancy CW. 2022 AHA/ACC Key Data Elements and Definitions for Cardiovascular and Noncardiovascular Complications of COVID-19: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Data Standards. Circ Cardiovasc Qual Outcomes 2022; 15:e000111. [PMID: 35737748 PMCID: PMC9297692 DOI: 10.1161/hcq.0000000000000111] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
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Sirohiya P, Vig S, Mathur T, Meena JK, Panda S, Goswami G, Gupta R, Konkimalla A, Kondamudi D, Gupta N, Ratre BK, Singh R, Kumar B, Pandit A, Sikka K, Thakar A, Bhatnagar S. Airway management, procedural data, and in-hospital mortality records of patients undergoing surgery for mucormycosis associated with coronavirus disease (COVID-19). J Mycol Med 2022; 32:101307. [PMID: 35849869 PMCID: PMC9250164 DOI: 10.1016/j.mycmed.2022.101307] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Revised: 05/04/2022] [Accepted: 07/01/2022] [Indexed: 12/02/2022]
Abstract
Purpose Although unexpected airway difficulties are reported in patients with mucormycosis, the literature on airway management in patients with mucormycosis associated with Coronavirus disease is sparse. Methods In this retrospective case record review of 57 patients who underwent surgery for mucormycosis associated with coronavirus disease, we aimed to evaluate the demographics, airway management, procedural data, and in-hospital mortality records. Results Forty-one (71.9%) patients had a diagnosis of sino-nasal mucormycosis, fourteen (24.6%) patients had a diagnosis of rhino-orbital mucormycosis, and 2 (3.5%) patients had a diagnosis of palatal mucormycosis. A total of 44 (77.2%) patients had co-morbidities. The most common co-morbidities were diabetes mellitus in 42 (73.6%) patients, followed by hypertension in 21 (36.8%) patients, and acute kidney injury in 14 (28.1%) patients. We used the intubation difficulty scale score to assess intubating conditions. Intubation was easy to slightly difficult in 53 (92.9%) patients. In our study, mortality occurred in 7 (12.3%) patients. The median (range) mortality time was 60 (27–74) days. The median (range) time to hospital discharge was 53.5 (10–85) days. The median [interquartile range] age of discharged versus expired patients was 47.5 [41,57.5] versus 64 [47,70] years (P = 0.04), and median (interquartile range) D-dimer levels in discharged versus expired patients was 364 [213, 638] versus 2448 [408,3301] ng/mL (P = 0.03). Conclusion In patients undergoing surgery for mucormycosis associated with the coronavirus disease, airway management was easy to slightly difficult in most patients. Perioperative complications can be minimized by taking timely and precautionary measures.
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Affiliation(s)
- Prashant Sirohiya
- Department of Onco-anaesthesia and Palliative Medicine, All India Institute of Medical Sciences, New Delhi, India
| | - Saurabh Vig
- Department of Onco-anaesthesia and Palliative Medicine, All India Institute of Medical Sciences, New Delhi, India
| | - Tanmay Mathur
- Department of Onco-anaesthesia and Palliative Medicine, All India Institute of Medical Sciences, New Delhi, India
| | - Jitendra Kumar Meena
- Department of Preventive Oncology, All India Institute of Medical Sciences, New Delhi, India
| | - Smriti Panda
- Department of Otorhinolaryngology and Head and Neck Surgery, All India Institute of Medical Sciences, New Delhi, India
| | - Gitartha Goswami
- Department of Onco-anaesthesia and Palliative Medicine, All India Institute of Medical Sciences, New Delhi, India
| | - Raghav Gupta
- Department of Onco-anaesthesia and Palliative Medicine, All India Institute of Medical Sciences, New Delhi, India
| | - Abhilash Konkimalla
- Department of Otorhinolaryngology and Head and Neck Surgery, All India Institute of Medical Sciences, New Delhi, India
| | - Dheeraj Kondamudi
- Department of Otorhinolaryngology and Head and Neck Surgery, All India Institute of Medical Sciences, New Delhi, India
| | - Nishkarsh Gupta
- Department of Onco-anaesthesia and Palliative Medicine, All India Institute of Medical Sciences, New Delhi, India
| | - Brajesh Kumar Ratre
- Department of Onco-anaesthesia and Palliative Medicine, All India Institute of Medical Sciences, New Delhi, India
| | - Ram Singh
- Department of Onco-anaesthesia and Palliative Medicine, All India Institute of Medical Sciences, New Delhi, India
| | - Balbir Kumar
- Department of Onco-anaesthesia and Palliative Medicine, All India Institute of Medical Sciences, New Delhi, India
| | - Anuja Pandit
- Department of Onco-anaesthesia and Palliative Medicine, All India Institute of Medical Sciences, New Delhi, India
| | - Kapil Sikka
- Department of Otorhinolaryngology and Head and Neck Surgery, All India Institute of Medical Sciences, New Delhi, India
| | - Alok Thakar
- Department of Otorhinolaryngology and Head and Neck Surgery, All India Institute of Medical Sciences, New Delhi, India
| | - Sushma Bhatnagar
- Department of Onco-anaesthesia and Palliative Medicine, All India Institute of Medical Sciences, New Delhi, India.
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Gorog DA, Storey RF, Gurbel PA, Tantry US, Berger JS, Chan MY, Duerschmied D, Smyth SS, Parker WAE, Ajjan RA, Vilahur G, Badimon L, Berg JMT, Cate HT, Peyvandi F, Wang TT, Becker RC. Current and novel biomarkers of thrombotic risk in COVID-19: a Consensus Statement from the International COVID-19 Thrombosis Biomarkers Colloquium. Nat Rev Cardiol 2022; 19:475-495. [PMID: 35027697 PMCID: PMC8757397 DOI: 10.1038/s41569-021-00665-7] [Citation(s) in RCA: 174] [Impact Index Per Article: 58.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/16/2021] [Indexed: 02/06/2023]
Abstract
Coronavirus disease 2019 (COVID-19) predisposes patients to thrombotic and thromboembolic events, owing to excessive inflammation, endothelial cell activation and injury, platelet activation and hypercoagulability. Patients with COVID-19 have a prothrombotic or thrombophilic state, with elevations in the levels of several biomarkers of thrombosis, which are associated with disease severity and prognosis. Although some biomarkers of COVID-19-associated coagulopathy, including high levels of fibrinogen and D-dimer, were recognized early during the pandemic, many new biomarkers of thrombotic risk in COVID-19 have emerged. In this Consensus Statement, we delineate the thrombotic signature of COVID-19 and present the latest biomarkers and platforms to assess the risk of thrombosis in these patients, including markers of platelet activation, platelet aggregation, endothelial cell activation or injury, coagulation and fibrinolysis as well as biomarkers of the newly recognized post-vaccine thrombosis with thrombocytopenia syndrome. We then make consensus recommendations for the clinical use of these biomarkers to inform prognosis, assess disease acuity, and predict thrombotic risk and in-hospital mortality. A thorough understanding of these biomarkers might aid risk stratification and prognostication, guide interventions and provide a platform for future research.
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Affiliation(s)
- Diana A Gorog
- National Heart and Lung Institute, Imperial College, London, UK.
- School of Life and Medical Sciences, University of Hertfordshire, Hatfield, UK.
| | - Robert F Storey
- Cardiovascular Research Unit, Department of Infection, Immunity & Cardiovascular Disease, University of Sheffield, Sheffield, UK
| | - Paul A Gurbel
- Sinai Center for Thrombosis Research and Drug Development, Sinai Hospital of Baltimore, Baltimore, MD, USA
| | - Udaya S Tantry
- Sinai Center for Thrombosis Research and Drug Development, Sinai Hospital of Baltimore, Baltimore, MD, USA
| | - Jeffrey S Berger
- New York University Grossman School of Medicine, New York, NY, USA
| | - Mark Y Chan
- Yong Loo-Lin School of Medicine, National University of Singapore, Singapore, Singapore
- National University Heart Centre, Singapore, Singapore
| | - Daniel Duerschmied
- Cardiology and Angiology I and Medical Intensive Care, Faculty of Medicine, Medical Center, University of Freiburg, Freiburg im Breisgau, Germany
- Cardiology, Medical Intensive Care, Angiology and Haemostaseology, University Medical Centre Mannheim, Mannheim, Germany
| | - Susan S Smyth
- UAMS College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, USA
| | - William A E Parker
- Cardiovascular Research Unit, Department of Infection, Immunity & Cardiovascular Disease, University of Sheffield, Sheffield, UK
| | - Ramzi A Ajjan
- Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK
| | - Gemma Vilahur
- Cardiovascular Research Center-ICCC, Research Institute - Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, Barcelona, Spain
- CiberCV, Institute Carlos III, Madrid, Spain
| | - Lina Badimon
- Cardiovascular Research Center-ICCC, Research Institute - Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, Barcelona, Spain
- CiberCV, Institute Carlos III, Madrid, Spain
- Universitat Autonoma de Barcelona, Barcelona, Spain
| | | | - Hugo Ten Cate
- Cardiovascular Research Institute Maastricht (CARIM) and Thrombosis Expertise Center, Maastricht University Medical Center, Maastricht, Netherlands
- Center for Thrombosis and Haemostasis, University Medical Center of Gutenberg University, Mainz, Germany
| | - Flora Peyvandi
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy
- Università degli Studi di Milano, Department of Pathophysiology and Transplantation, Milan, Italy
| | - Taia T Wang
- Department of Medicine, Division of Infectious Diseases, Stanford University, Stanford, CA, USA
- Department of Microbiology and Immunology, Stanford University, Stanford, CA, USA
- Chan Zuckerberg Biohub, San Francisco, CA, USA
| | - Richard C Becker
- Heart, Lung and Vascular Institute, University of Cincinnati College of Medicine, Cincinnati, OH, USA
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Postacute elevation of D-dimer levels in severe acute respiratory syndrome coronavirus 2-positive nonhospitalized patients with mild symptoms. Blood Coagul Fibrinolysis 2022; 33:285-287. [PMID: 35703244 PMCID: PMC9470043 DOI: 10.1097/mbc.0000000000001111] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
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Güler A, Gürbak İ, Panç C, Güner A, Ertürk M. Frequency and predictors of no-reflow phenomenon in patients with COVID-19 presenting with ST-segment elevation myocardial infarction. Acta Cardiol 2022; 77:313-321. [PMID: 34053402 DOI: 10.1080/00015385.2021.1931638] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
OBJECTIVES Thrombotic process is triggered in the course of Coronavirus disease-2019 (COVID-19), which is a global pandemic, and both arterial and venous systems are affected. ST-elevation myocardial infarction (STEMI) that may develop in these patients may cause more complicated results with the effect of thrombosis burden. Our aim in this study is to determine the frequency of no-reflow phenomenon in COVID-19 patients with STEMI and to determine the factors that predict this complication. METHODS In this study, which is a single-centre, retrospective and observational, a total of 126 patients who underwent primary percutaneous coronary intervention (pPCI) in our centre due to STEMI between 11 March 2020 and 10 January 2021 were evaluated. Patients were divided into two groups according to the presence of COVID-19 infection. RESULTS While 62 patients were in the COVID-19 (+) group, 64 patients were evaluated in the COVID-19 (-) group. When the two groups are compared, C-reactive protein, D-dimer, ferritin and neutrophil-lymphocyte ratio (NLR) were significantly higher, and the lymphocyte count was significantly lower in the COVID-19 (+) group. No-reflow was numerically higher in patients with COVID-19. In multivariable analysis, D-dimer and NLR were found to be independent predictors of no-reflow phenomenon in COVID-19 patients. CONCLUSIONS Although the no-reflow phenomenon was numerically higher in COVID-19 patients who underwent pPCI due to STEMI compared to the non-COVID group, no statistical difference was found in our study. However, NLR and D-dimer have been identified as independent predictors of no-reflow development risk in COVID-19 patients.
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Affiliation(s)
- Arda Güler
- Department of Cardiology, Health Sciences University, Mehmet Akif Ersoy Thoracic and Cardiovascular Surgery Training and Research Hospital, Istanbul, Turkey
| | - İsmail Gürbak
- Department of Cardiology, Health Sciences University, Mehmet Akif Ersoy Thoracic and Cardiovascular Surgery Training and Research Hospital, Istanbul, Turkey
| | - Cafer Panç
- Department of Cardiology, Health Sciences University, Mehmet Akif Ersoy Thoracic and Cardiovascular Surgery Training and Research Hospital, Istanbul, Turkey
| | - Ahmet Güner
- Department of Cardiology, Health Sciences University, Mehmet Akif Ersoy Thoracic and Cardiovascular Surgery Training and Research Hospital, Istanbul, Turkey
| | - Mehmet Ertürk
- Department of Cardiology, Health Sciences University, Mehmet Akif Ersoy Thoracic and Cardiovascular Surgery Training and Research Hospital, Istanbul, Turkey
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Al-Biltagi M, Hantash EM, El-Shanshory MR, Badr EA, Zahra M, Anwar MH. Plasma D-dimer level in early and late-onset neonatal sepsis. World J Crit Care Med 2022; 11:139-148. [PMID: 36331988 PMCID: PMC9136721 DOI: 10.5492/wjccm.v11.i3.139] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2021] [Revised: 03/09/2022] [Accepted: 04/21/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Neonatal sepsis is a life-threatening disease. Early diagnosis is essential, but no single marker of infection has been identified. Sepsis activates a coagulation cascade with simultaneous production of the D-dimers due to lysis of fibrin. D-dimer test reflects the activation of the coagulation system.
AIM To assess the D-dimer plasma level, elaborating its clinicopathological value in neonates with early-onset and late-onset neonatal sepsis.
METHODS The study was a prospective cross-sectional study that included ninety neonates; divided into three groups: Group I: Early-onset sepsis (EOS); Group II: Late-onset sepsis (LOS); and Group III: Control group. We diagnosed neonatal sepsis according to our protocol. C-reactive protein (CRP) and D-dimer assays were compared between EOS and LOS and correlated to the causative microbiological agents.
RESULTS D-dimer was significantly higher in septic groups with a considerably higher number of cases with positive D-dimer. Neonates with LOS had substantially higher levels of D-dimer than EOS, with no significant differences in CRP. Neonates with LOS had a significantly longer hospitalization duration and higher gram-negative bacteriemia and mortality rates than EOS (P < 0.01). Gram-negative bacteria have the highest D-dimer levels (Acinetobacter, Klebsiella, and Pseudomonas) and CRP (Serratia, Klebsiella, and Pseudomonas); while gram-positive sepsis was associated with relatively lower levels. D-dimer had a significant negative correlation with hemoglobin level and platelet count; and a significant positive correlation with CRP, hospitalization duration, and mortality rates. The best-suggested cut-off point for D-dimer in neonatal sepsis was 0.75 mg/L, giving a sensitivity of 72.7% and specificity of 86.7%. The D-dimer assay has specificity and sensitivity comparable to CRP in the current study.
CONCLUSION The current study revealed a significant diagnostic value for D-dimer in neonatal sepsis. D-dimer can be used as an adjunct to other sepsis markers to increase the sensitivity and specificity of diagnosing neonatal sepsis.
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Affiliation(s)
- Mohammed Al-Biltagi
- Department of Pediatrics, Faculty of Medicine, Tanta University, Tanta 31511, Algharbia, Egypt
- Department of Pediatrics, University Medical Center, Arabian Gulf University, Manama 26671, Manama, Bahrain
- Department of Pediatrics, University Medical Center, Bahrain, Dr. Sulaiman Al Habib Medical Group, KSA, Manama 26671, Manama, Bahrain
| | - Ehab M Hantash
- Department of Anatomy, Faculty of Medicine, Tanta University, Tanta 31511, Alghrabia, Egypt
- Neonatology Unit, Department of Pediatrics, Dr. Sulaiman Al Habib Medical Group, Riyadh 11636, Riyadh, Saudi Arabia
| | | | - Enayat Aly Badr
- Department of Clinical Pathology, Faculty of Medicine, Tanta University, Tanta 31511, Alghrabia, Egypt
| | - Mohamed Zahra
- Department of Clinical Pathology, Faculty of Medicine, Tanta University, Tanta 31511, Alghrabia, Egypt
| | - Manar Hany Anwar
- Department of Clinical Pathology, Ministry of Health, Egypt, Tanta 31511, Alghrabia, Egypt
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Leretter M, Vulcanescu D, Horhat F, Matichescu A, Rivis M, Rusu LC, Roi A, Racea R, Badea I, Dehelean C, Mocanu A, Horhat D. COVID‑19: Main findings after a year and half of unease and the proper scientific progress (Review). Exp Ther Med 2022; 23:424. [PMID: 35601072 PMCID: PMC9117952 DOI: 10.3892/etm.2022.11350] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Accepted: 11/17/2021] [Indexed: 11/21/2022] Open
Abstract
Since the emergence of the disease in late December 2019, numerous studies have been published to date regarding clinical, laboratory and treatment aspects associated with COVID-19. The present study attempts to compare and unify the clinical, para-clinical and therapeutic aspects that have come to light regarding coronavirus disease-19 (COVID 19), mainly in adults. Between April 2020 and September 2021, a comprehensive systematic literature review was performed, which we added to from our own medical experiences. The search was performed on the PubMed, Scopus and Google Scholar databases, comprising studies with analyzable data that were identified alongside studies and documents containing general scientific data. All published studies were written in English, and were from different countries. A 95% confidence interval (CI95) was also calculated for almost each study using the Wilson formula. When compared with preliminary reports between December 2019 and January 2020, the most frequent symptoms were still identified as being fever (68.6%; CI95: 67.5-69.7) and cough (72.7%; CI95: 71.7-73.8). Nevertheless, asymptomatic cases also increased (by 21.4%; CI95: 16.6-27.1). Severe and critical cases accounted for 10.4% (CI95: 9.6-11.1) of all cases. The mean fatality rate was found to be 4% (CI95: 3.6-4.5). The primary co-morbidity found was hypertension (28.9%; CI95: 27-30.8), followed by other underlying cardiovascular diseases (15.4%; CI95: 13.9-16.9) and diabetes (14.5%; CI95: 13.1-16.1). The majority of studies showed lower white blood cell numbers with neutropenia and lymphopenia, and lower platelet levels. The levels of the biomarkers C-reaction protein and erythrocyte sedimentation rate were positive in all studied cases alongside other lab tests, such as examining the D-dimer levels and those of other hepatic, cardiac and renal injury markers. The procalcitonin level was also found to be elevated in many cases, resulting in high usage of antibiotics (83.7%; CI95: 81.2-85.9). Approximately 31.6% (CI95: 29.1-34.1) of the patients required non-invasive ventilation, whereas 9.9% (CI95: 8.1-12.1) of the patients were intubated or placed on extracorporeal membrane oxygenation. The most used antivirals were ribavirin (67.3%; CI95: 63.4-70.9), oseltamivir (52.5%; CI95: 49.4-55.5) and Arbidol™ (34.5%; CI95: 32-37.1). General admittance to the intensive care unit was ~7.2% (CI95: 6.5-7.9) of patients.
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Affiliation(s)
- Marius Leretter
- Department of Prosthodontics, Multidisciplinary Center for Research, Evaluation, Diagnosis and Therapies in Oral Medicine, ‘Victor Babeș’ University of Medicine and Pharmacy, 300041 Timisoara, Romania
| | - Dan Vulcanescu
- Department of Microbiology, Multidisciplinary Research Center on Antimicrobial Resistance (MULTI‑REZ), ‘Victor Babeș’ University of Medicine and Pharmacy, 300041 Timisoara, Romania
| | - Florin Horhat
- Department of Microbiology, Multidisciplinary Research Center on Antimicrobial Resistance (MULTI‑REZ), ‘Victor Babeș’ University of Medicine and Pharmacy, 300041 Timisoara, Romania
| | - Anamaria Matichescu
- Department of Preventive Dentistry, Community and Oral Health, ‘Victor Babeș’ University of Medicine and Pharmacy, 300041 Timisoara, Romania
| | - Mircea Rivis
- Department of Anesthesiology and Oral Surgery, Multidisciplinary Center for Research, Evaluation, Diagnosis and Therapies in Oral Medicine, ‘Victor Babeș’ University of Medicine and Pharmacy, 300041 Timisoara, Romania
| | - Laura-Cristina Rusu
- Department of Oral Pathology, Multidisciplinary Center for Research, Evaluation, Diagnosis and Therapies in Oral Medicine, ‘Victor Babeș’ University of Medicine and Pharmacy, 300041 Timisoara, Romania
| | - Alexandra Roi
- Department of Oral Pathology, Multidisciplinary Center for Research, Evaluation, Diagnosis and Therapies in Oral Medicine, ‘Victor Babeș’ University of Medicine and Pharmacy, 300041 Timisoara, Romania
| | - Robert Racea
- Department of Oral Pathology, Multidisciplinary Center for Research, Evaluation, Diagnosis and Therapies in Oral Medicine, ‘Victor Babeș’ University of Medicine and Pharmacy, 300041 Timisoara, Romania
| | - Ioana Badea
- Department of Oral Pathology, Multidisciplinary Center for Research, Evaluation, Diagnosis and Therapies in Oral Medicine, ‘Victor Babeș’ University of Medicine and Pharmacy, 300041 Timisoara, Romania
| | - Cristina Dehelean
- Department of Toxicology, Research Center for Pharmaco‑Toxicological Evaluation, ‘Victor Babeș’ University of Medicine and Pharmacy, 300041 Timisoara, Romania
| | - Alexandra Mocanu
- Department XIII, Discipline of Infectious Diseases, ‘Victor Babeș’ University of Medicine and Pharmacy, 300041 Timisoara, Romania
| | - Delia Horhat
- Department of Otorhinolaryngology, ‘Victor Babeș’ University of Medicine and Pharmacy, 300041 Timisoara, Romania
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Pérez-García N, García-González J, Requena-Mullor M, Rodríguez-Maresca MÁ, Alarcón-Rodríguez R. Comparison of Analytical Values D-Dimer, Glucose, Ferritin and C-Reactive Protein of Symptomatic and Asymptomatic COVID-19 Patients. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:5354. [PMID: 35564749 PMCID: PMC9102188 DOI: 10.3390/ijerph19095354] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/16/2022] [Revised: 04/19/2022] [Accepted: 04/25/2022] [Indexed: 02/04/2023]
Abstract
Those infected by COVID-19 develop various kinds of complications with varying degrees of severity. For this reason, it is necessary to evaluate its analytical values to predict and reduce the risks and complications derived from this pathology. A cross-sectional study was carried out a population in Almeria (south-eastern Spain) who had a positive Polymerase Chain Reaction test result from 1 March 2020 to 30 November 2020. The study involved 4575 patients, with 1346 who were asymptomatic, 1653 mildly symptomatic (no hospitalisation needed) and 1576 severely symptomatic (symptomatic patients hospitalised). Laboratory values for D-dimer, glucose, serum ferritin, and C-reactive protein were analysed. The mean age of the participants in the study was 53.60 (16.89) years old. A total of 70.6% of the patients were symptomatic, of which 36.1% had mild symptoms. For all of the laboratory predictors analysed (D-dimer, glucose, serum ferritin, and C-reactive protein), it was found that severe alterations in the parameters were more frequent in severely symptomatic patients with statistically significant differences (p < 0.001), although these alterations also occurred in asymptomatic patients. Age correlated with analytical values (D-dimer, glucose, serum ferritin, and C-reactive protein) with statistically significant differences. Patients with severe symptoms presented alterations in the analytical values of D-dimer, glucose, serum ferritin, and C-reactive protein. Asymptomatic patients presented alterations in the analysed parameters, though with less frequency and severity than patients with severe symptoms.
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Affiliation(s)
| | - Jessica García-González
- Department of Nursing, Physiotherapy and Medicine, University of Almeria, 04120 Almería, Spain; (M.R.-M.); (R.A.-R.)
| | - Mar Requena-Mullor
- Department of Nursing, Physiotherapy and Medicine, University of Almeria, 04120 Almería, Spain; (M.R.-M.); (R.A.-R.)
| | | | - Raquel Alarcón-Rodríguez
- Department of Nursing, Physiotherapy and Medicine, University of Almeria, 04120 Almería, Spain; (M.R.-M.); (R.A.-R.)
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Lumish HS, Kim E, Selvaggi C, Cao T, Gupta A, Foulkes AS, Reilly MP. Biomarkers of Cardiac Injury, Renal Injury, and Inflammation Are Strong Mediators of Sex-Associated Death in COVID-19. Front Cardiovasc Med 2022; 9:809997. [PMID: 35548417 PMCID: PMC9081502 DOI: 10.3389/fcvm.2022.809997] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Accepted: 03/29/2022] [Indexed: 01/08/2023] Open
Abstract
BackgroundStudies examining outcomes among individuals with COronaVIrus Disease 2019 (COVID-19) have consistently demonstrated that men have worse outcomes than women, with a higher incidence of myocardial injury, respiratory failure, and death. However, mechanisms of higher morbidity and mortality among men remain poorly understood. We aimed to identify mediators of the relationship between sex and COVID-19-associated mortality.MethodsPatients hospitalized at two quaternary care facilities, New York Presbyterian Hospital (CUIMC/NYPH) and Massachusetts General Hospital (MGH), for SARS-CoV-2 infection between February and May 2020 were included. Five independent biomarkers were identified as mediators of sex effects, including high-sensitivity cardiac troponin T (hs-cTNT), high sensitivity C-reactive protein (hs-CRP), ferritin, D-dimer, and creatinine.ResultsIn the CUIMC/NYPH cohort (n = 2,626, 43% female), male sex was associated with significantly greater mortality (26 vs. 21%, p = 0.0146) and higher peak hs-cTNT, hs-CRP, ferritin, D-dimer, and creatinine (p < 0.001). The effect of male sex on the primary outcome of death was partially mediated by peak values of all five biomarkers, suggesting that each pathophysiological pathway may contribute to increased risk of death in men. Hs-cTnT, creatinine, and hs-CRP were the strongest mediators. Findings were highly consistent in the MGH cohort with the exception of D-dimer.ConclusionsThis study suggests that the effect of sex on COVID-19 outcomes is mediated by cardiac and kidney injury, as well as underlying differences in inflammation and iron metabolism. Exploration of these specific pathways may facilitate sex-directed diagnostic and therapeutic strategies for patients with COVID-19 and provides a framework for the study of sex differences in other complex diseases.
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Affiliation(s)
- Heidi S. Lumish
- Division of Cardiology, Columbia University, New York, NY, United States
- *Correspondence: Heidi S. Lumish
| | - Eunyoung Kim
- Division of Cardiology, Columbia University, New York, NY, United States
| | - Caitlin Selvaggi
- Biostatistics Center, Massachusetts General Hospital, Boston, MA, United States
- Department of Medicine, Harvard Medical School, Boston, MA, United States
- Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA, United States
| | - Tingyi Cao
- Biostatistics Center, Massachusetts General Hospital, Boston, MA, United States
- Department of Medicine, Harvard Medical School, Boston, MA, United States
- Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA, United States
| | - Aakriti Gupta
- Division of Interventional Cardiology, Cedars-Sinai Medical Center, Los Angeles, CA, United States
| | - Andrea S. Foulkes
- Biostatistics Center, Massachusetts General Hospital, Boston, MA, United States
- Department of Medicine, Harvard Medical School, Boston, MA, United States
- Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA, United States
| | - Muredach P. Reilly
- Division of Cardiology, Columbia University, New York, NY, United States
- Irving Institute for Clinical and Translational Research, Columbia University, New York, NY, United States
- Muredach P. Reilly
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Kouhpayeh H. Clinical features predicting COVID-19 mortality risk. Eur J Transl Myol 2022; 32:10268. [PMID: 35421918 PMCID: PMC9295175 DOI: 10.4081/ejtm.2022.10268] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Accepted: 11/23/2021] [Indexed: 12/15/2022] Open
Abstract
Currently, the world is involved by a pandemic of severe acute respiratory syndrome coronavirus 2 (SARS CoV-2), which has been responsible for the deaths of hundreds of thousands of people so far. The consequences of infection with SARS-CoV-2 vary widely from asymptomatic to severe. Considering the increasing prevalence of different types of virus and acute infection with this disease, strategies to prevent mortality from COVID-19 should be seriously analyzed. In this study, the epidemiological, clinical and laboratory characteristics of patients with COVID-19 were investigated in order to identify risk factors for mortality. Chronic diseases such as chronic kidney disease (CKD), COPD, diabetes, hypertension, cardiovascular disease (CVD), cancer, increased D-dimer, male gender, old age, smoking and obesity are among the deadly risk factors associated COVID-19. Furthermore, lymphopenia and neutrophilia are often present in patients with SARS-CoV-2, and the ratio of absolute neutrophils to lymphocytes (NLR) was significantly increased in patients without bacterial infection. These findings could be used in the future to control and prevent disease, because timely identification of patients with risk of COVID-19 is important to provide better treatment strategies for reduction of mortality.
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Affiliation(s)
- Hamidreza Kouhpayeh
- Tropical and Infectious Diseases Department, Zahedan University of Medical Sciences, Zahedan, Iran; Zahedan University of Medical Sciences Research Center, Emam Ali Hospital, Zahedan.
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Esmailian M, Vakili Z, Nasr-Esfahani M, Heydari F, Masoumi B. D-dimer Levels in Predicting Severity of Infection and Outcome in Patients with COVID-19. TANAFFOS 2022; 21:419-433. [PMID: 37583776 PMCID: PMC10423863] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Subscribe] [Scholar Register] [Received: 01/20/2022] [Accepted: 06/07/2022] [Indexed: 08/17/2023]
Abstract
COVID-19 disease began to spread all around the world in December 2019 until now; and in the early stage it may be related to high D-dimer level that indicates coagulation pathways and thrombosis activation that can be affected by some underlying diseases including diabetes, stroke, cancer, and pregnancy and it also can be associated with Chronic obstructive pulmonary disease (COPD). The aim of this article was to analyze D-dimer levels in COVID-19 patients, as D-dimer level is one of the measures to detect the severity and outcomes of COVID-19. According to the results of this study, there is a higher level of D-dimer as well as concentrations of fibrinogen in the disease onset and it seems that the poor prognosis is linked to a 3 to 4-fold increase in D-dimer levels. It is also shown that 76% of the patients with ≥1 D-dimer measurement, had elevated D-dimer and were more likely to have critical illness than those with normal D-dimer. There was an increase in the rates of adverse outcomes with higher D-dimer of more than 2000 ng/mL and it is associated with the highest risk of death at 47%, thrombotic event at 37.8%, and critical illness at 66%. It also found that diabetes and COPD had the strongest association with death in COVID-19. So, it is necessary to measure the D-dimer levels and parameters of coagulation from the beginning as well as pay attention to comorbidities that can help control and management of COVID-19 disease.
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Affiliation(s)
- Mehrdad Esmailian
- Department of Emergency Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Zohreh Vakili
- Department of Emergency Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | | | - Farhad Heydari
- Department of Emergency Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Babak Masoumi
- Department of Emergency Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
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Yildiz Gulhan P, Eroz R, Ataoglu O, İnce N, Davran F, Öztürk CE, Gamsızkan Z, Balbay OA. The evaluation of both the expression and serum protein levels of Caspase-3 gene in patients with different degrees of SARS-CoV2 infection. J Med Virol 2022; 94:897-905. [PMID: 34585746 PMCID: PMC8662079 DOI: 10.1002/jmv.27362] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2021] [Revised: 09/18/2021] [Accepted: 09/27/2021] [Indexed: 01/15/2023]
Abstract
To evaluate the effects of Caspase-3 (CASP3) gene expression and serum levels on preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. A total of 41 individuals (male: 21; female: 20) with SARS-CoV-2 infection were included in the current study. Hemograms were examined from patient blood samples, and CASP3 gene expression levels were detected. Also, human CASP3 levels were determined from the serum samples of patients. The mean age of patients was 56.220 ± 18.937 years. Significant differences were detected among all groups for CASP3 2 - ΔΔ C t (p = 0.014) and CASP3 concentration (p = 0.024). The relationship between CASP3 2 - ΔΔ C t levels and hemoglobin (p = 0.023), between CASP3 2 - ΔΔ C t levels and C-reactive protein (CRP) (p = 0.001), between CASP3 2 - ΔΔ C t levels and ferritin (p = 0.003), between CASP3 2 - ΔΔ C t levels and lactate dehydrogenase (p = 0.001), and between CASP3 2 - ΔΔ C t levels and SpO2 (p = 0.006) were statistically significant. Also, the relationship between CASP3 concentration levels and SpO2 was statistically significant (p < 0.046). The CASP3 gene and/or its products have an important function to prevent injury caused by SARS-CoV-2 infection. They play crucial roles in maintaining cellular homeostasis and viability. Perhaps CASP3 levels may provide information about the severity of the disease.
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Affiliation(s)
| | - Recep Eroz
- Department of Medical GeneticsDuzce University Medical FacultyDuzceTurkey
| | | | - Nevin İnce
- Department of Infection DiseasesDuzce University Medical FacultyDuzceTurkey
| | - Fatih Davran
- Department of BiochemistryDuzce University Medical FacultyDuzceTurkey
| | | | - Zerrin Gamsızkan
- Department of Family MedicineDuzce University Medical FacultyDuzceTurkey
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46
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Kell DB, Laubscher GJ, Pretorius E. A central role for amyloid fibrin microclots in long COVID/PASC: origins and therapeutic implications. Biochem J 2022; 479:537-559. [PMID: 35195253 PMCID: PMC8883497 DOI: 10.1042/bcj20220016] [Citation(s) in RCA: 130] [Impact Index Per Article: 43.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Revised: 02/08/2022] [Accepted: 02/09/2022] [Indexed: 12/15/2022]
Abstract
Post-acute sequelae of COVID (PASC), usually referred to as 'Long COVID' (a phenotype of COVID-19), is a relatively frequent consequence of SARS-CoV-2 infection, in which symptoms such as breathlessness, fatigue, 'brain fog', tissue damage, inflammation, and coagulopathies (dysfunctions of the blood coagulation system) persist long after the initial infection. It bears similarities to other post-viral syndromes, and to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Many regulatory health bodies still do not recognize this syndrome as a separate disease entity, and refer to it under the broad terminology of 'COVID', although its demographics are quite different from those of acute COVID-19. A few years ago, we discovered that fibrinogen in blood can clot into an anomalous 'amyloid' form of fibrin that (like other β-rich amyloids and prions) is relatively resistant to proteolysis (fibrinolysis). The result, as is strongly manifested in platelet-poor plasma (PPP) of individuals with Long COVID, is extensive fibrin amyloid microclots that can persist, can entrap other proteins, and that may lead to the production of various autoantibodies. These microclots are more-or-less easily measured in PPP with the stain thioflavin T and a simple fluorescence microscope. Although the symptoms of Long COVID are multifarious, we here argue that the ability of these fibrin amyloid microclots (fibrinaloids) to block up capillaries, and thus to limit the passage of red blood cells and hence O2 exchange, can actually underpin the majority of these symptoms. Consistent with this, in a preliminary report, it has been shown that suitable and closely monitored 'triple' anticoagulant therapy that leads to the removal of the microclots also removes the other symptoms. Fibrin amyloid microclots represent a novel and potentially important target for both the understanding and treatment of Long COVID and related disorders.
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Affiliation(s)
- Douglas B. Kell
- Department of Biochemistry and Systems Biology, Institute of Systems, Molecular and Integrative Biology, Faculty of Health and Life Sciences, University of Liverpool, Liverpool L69 7ZB, U.K
- The Novo Nordisk Foundation Centre for Biosustainability, Technical University of Denmark, Kemitorvet 200, 2800 Kgs Lyngby, Denmark
- Department of Physiological Sciences, Faculty of Science, Stellenbosch University, Stellenbosch Private Bag X1 Matieland, 7602, South Africa
| | | | - Etheresia Pretorius
- Department of Physiological Sciences, Faculty of Science, Stellenbosch University, Stellenbosch Private Bag X1 Matieland, 7602, South Africa
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47
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Arachchillage DJ, Rajakaruna I, Odho Z, Crossette-Thambiah C, Nicolson PLR, Roberts LN, Allan C, Lewis S, Riat R, Mounter P, Lynch C, Langridge A, Oakes R, Aung N, Drebes A, Dutt T, Raheja P, Delaney A, Essex S, Lowe G, Sutton D, Lentaigne C, Sayar Z, Kilner M, Everington T, Shapiro S, Alikhan R, Szydlo R, Makris M, Laffan M. Clinical outcomes and the impact of prior oral anticoagulant use in patients with coronavirus disease 2019 admitted to hospitals in the UK - a multicentre observational study. Br J Haematol 2022; 196:79-94. [PMID: 34500500 DOI: 10.1111/bjh.17787] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2021] [Accepted: 08/07/2021] [Indexed: 12/22/2022]
Abstract
Coagulation dysfunction and thrombosis are major complications in patients with coronavirus disease 2019 (COVID-19). Patients on oral anticoagulants (OAC) prior to diagnosis of COVID-19 may therefore have better outcomes. In this multicentre observational study of 5 883 patients (≥18 years) admitted to 26 UK hospitals between 1 April 2020 and 31 July 2020, overall mortality was 29·2%. Incidences of thrombosis, major bleeding (MB) and multiorgan failure (MOF) were 5·4%, 1·7% and 3·3% respectively. The presence of thrombosis, MB, or MOF was associated with a 1·8, 4·5 or 5·9-fold increased risk of dying, respectively. Of the 5 883 patients studied, 83·6% (n = 4 920) were not on OAC and 16·4% (n = 963) were taking OAC at the time of admission. There was no difference in mortality between patients on OAC vs no OAC prior to admission when compared in an adjusted multivariate analysis [hazard ratio (HR) 1·05, 95% confidence interval (CI) 0·93-1·19; P = 0·15] or in an adjusted propensity score analysis (HR 0·92 95% CI 0·58-1·450; P = 0·18). In multivariate and adjusted propensity score analyses, the only significant association of no anticoagulation prior to diagnosis of COVID-19 was admission to the Intensive-Care Unit (ICU) (HR 1·98, 95% CI 1·37-2·85). Thrombosis, MB, and MOF were associated with higher mortality. Our results indicate that patients may have benefit from prior OAC use, especially reduced admission to ICU, without any increase in bleeding.
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Affiliation(s)
- Deepa J Arachchillage
- Centre for Haematology, Department of Immunology and Inflammation, Imperial College London, UK
- Department of Haematology, Imperial College Healthcare NHS Trust, UK
| | | | - Zain Odho
- Department of Biochemistry, Royal Brompton Hospital, London, UK
| | | | | | - Lara N Roberts
- King's College Hospital NHS Foundation Trust, London, UK
| | - Caroline Allan
- Department of Emergency Medicine, Aberdeen Royal Infirmary Aberdeen, Aberdeen, UK
| | - Sarah Lewis
- Department of Haematology, Aneurin Bevan Health Board, Abergavenny, UK
| | - Renu Riat
- Department of Haematology, Buckinghamshire Healthcare NHS Trust, Buckinghamshire, UK
| | - Philip Mounter
- Department of Haematology County Durham and Darlington, NHS Foundation Trust, Darlington, UK
| | - Ceri Lynch
- Department of Critical Care, Cwm Taf Morgannwg University Health Board, Cynon Taff, UK
| | - Alexander Langridge
- Department of Haematology, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
| | - Roderick Oakes
- Department of Haematology, North Cumbria Integrated Care NHS Foundation Trust, Carlisle, UK
| | - Nini Aung
- Department of Haematology, North Tees and Hartlepool NHS Foundation Trust, Hartlepool, UK
| | - Anja Drebes
- Department of Haematology, Royal Free London NHS Foundation Trust, London, UK
| | - Tina Dutt
- Department of Haematology, Royal Liverpool University Hospital, Liverpool, UK
| | - Priyanka Raheja
- Department of Haematology, The Royal London Hospital, London, UK
| | - Alison Delaney
- Department of Haematology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
| | - Sarah Essex
- Department of Haematology, South Tees Hospitals NHS Foundation Trust, Middlesbrough, UK
| | - Gillian Lowe
- Department of Haematology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - David Sutton
- Department of Haematology, University Hospitals of North Midlands NHS Trust, Stoke-on-Trent, UK
| | - Claire Lentaigne
- Department of Haematology, University Hospitals Plymouth NHS Trust Plymouth, UK
| | - Zara Sayar
- Department of Haematology, Whittington Health NHS Trust, London, UK
| | - Mari Kilner
- Department of Haematology, Northumbria Healthcare NHS Foundation Trust, Newcastle upon Tyne, UK
| | - Tamara Everington
- Department of Haematology, Hampshire Hospitals NHS Foundation Trust, Basingstoke, UK
| | - Susie Shapiro
- Department of Haematology, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - Raza Alikhan
- Haemophilia and Thrombosis Centre, University Hospital of Wales, Cardiff, UK
| | - Richard Szydlo
- Department of Immunology and Inflammation, Imperial College London, London, UK
| | - Michael Makris
- Department of Haematology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
| | - Michael Laffan
- Centre for Haematology, Department of Immunology and Inflammation, Imperial College London, UK
- Department of Haematology, Imperial College Healthcare NHS Trust, UK
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48
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Lehmann A, Prosch H, Zehetmayer S, Gysan MR, Bernitzky D, Vonbank K, Idzko M, Gompelmann D. Impact of persistent D-dimer elevation following recovery from COVID-19. PLoS One 2021; 16:e0258351. [PMID: 34710097 PMCID: PMC8553152 DOI: 10.1371/journal.pone.0258351] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2021] [Accepted: 09/26/2021] [Indexed: 01/30/2023] Open
Abstract
BACKGROUND Elevated D-dimer is known as predictor for severity of SARS-CoV2-infection. Increased D-dimer is associated with thromboembolic complications, but it is also a direct consequence of the acute lung injury seen in COVID-19 pneumonia. OBJECTIVES To evaluate the rate of persistent elevated D-dimer and its association with thromboembolic complications and persistent ground glass opacities (GGO) after recovery from COVID-19. METHODS In this post hoc analysis of a prospective multicenter trial, patients underwent blood sampling, measurement of diffusion capacity, blood gas analysis, and multidetector computed tomography (MDCT) scan following COVID-19. In case of increased D-dimer (>0,5 μg/ml), an additional contrast medium-enhanced CT was performed in absence of contraindications. Results were compared between patients with persistent D-dimer elevation and patients with normal D-dimer level. RESULTS 129 patients (median age 48.8 years; range 19-91 years) underwent D-Dimer assessment after a median (IQR) of 94 days (64-130) following COVID-19. D-dimer elevation was found in 15% (19/129) and was significantly more common in patients who had experienced a severe SARS-CoV2 infection that had required hospitalisation compared to patients with mild disease (p = 0.049). Contrast-medium CT (n = 15) revealed an acute pulmonary embolism in one patient and CTEPH in another patient. A significant lower mean pO2 (p = 0.015) and AaDO2 (p = 0.043) were observed in patients with persistent D-Dimer elevation, but the rate of GGO were similar in both patient groups (p = 0.33). CONCLUSION In 15% of the patients recovered from COVID-19, persistent D-dimer elevation was observed after a median of 3 months following COVID-19. These patients had experienced a more severe COVID and still presented more frequently a lower mean pO2 and AaDO2.
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Affiliation(s)
- Antje Lehmann
- Department of Medicine II, Division of Pulmonology, Medical University of Vienna, Vienna, Austria
- * E-mail:
| | - Helmut Prosch
- Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria
| | - Sonja Zehetmayer
- Center for Medical Statistics, Informatics, and Intelligent Systems, Medical University of Vienna, Vienna, Austria
| | - Maximilian Robert Gysan
- Department of Medicine II, Division of Pulmonology, Medical University of Vienna, Vienna, Austria
| | - Dominik Bernitzky
- Department of Medicine II, Division of Pulmonology, Medical University of Vienna, Vienna, Austria
| | - Karin Vonbank
- Department of Medicine II, Division of Pulmonology, Medical University of Vienna, Vienna, Austria
| | - Marco Idzko
- Department of Medicine II, Division of Pulmonology, Medical University of Vienna, Vienna, Austria
| | - Daniela Gompelmann
- Department of Medicine II, Division of Pulmonology, Medical University of Vienna, Vienna, Austria
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49
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Bowring MG, Wang Z, Xu Y, Betz J, Muschelli J, Garibaldi BT, Zeger SL. Outcome-Stratified Analysis of Biomarker Trajectories for Patients Infected With Severe Acute Respiratory Syndrome Coronavirus 2. Am J Epidemiol 2021; 190:2094-2106. [PMID: 33984860 PMCID: PMC8241476 DOI: 10.1093/aje/kwab138] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2020] [Revised: 04/12/2021] [Accepted: 05/04/2021] [Indexed: 12/23/2022] Open
Abstract
Longitudinal trajectories of vital signs and biomarkers during admission remain
poorly characterized for COVID-19 patients despite their potential to provide
critical insights about disease progression. We studied 1884 patients with
SARS-CoV2 infection from 3/4/2020-6/25/2020 within one Maryland hospital system
and used a retrospective longitudinal framework with linear mixed-effects models
to investigate relevant biomarker trajectories leading up to three critical
outcomes: mechanical ventilation, discharge, and death. Trajectories of four
vital signs (respiratory rate, SpO2/FiO2, pulse, and
temperature) and four lab values (C-reactive protein (CRP), absolute lymphocyte
count (ALC), estimated glomerular filtration rate (eGFR), and D-dimer) clearly
distinguished the trajectories of COVID-19 patients. Prior to any ventilation,
log-CRP, log-ALC, respiratory rate, and SpO2/FiO2
trajectories diverge approximately 8-10 days before discharge or death.
Following ventilation, log-CRP, log-ALC, respiratory rate,
SpO2/FiO2, and eGFR trajectories again diverge 10-20
days prior to death or discharge. Trajectories improved until discharge and
remained unchanged or worsened until death. Our approach characterizes the
distribution of biomarker trajectories leading up to competing outcomes of
discharge versus death. Moving forward, this model can contribute to quantifying
the joint probability of future biomarkers and outcomes provided clinical data
up to a given moment.
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Affiliation(s)
| | - Zitong Wang
- Department of Biostatistics Johns Hopkins University
Bloomberg School of Public Health, Baltimore Maryland
| | - Yizhen Xu
- Department of Biostatistics Johns Hopkins University
Bloomberg School of Public Health, Baltimore Maryland
| | - Joshua Betz
- Department of Biostatistics Johns Hopkins University
Bloomberg School of Public Health, Baltimore Maryland
| | - John Muschelli
- Department of Biostatistics Johns Hopkins University
Bloomberg School of Public Health, Baltimore Maryland
| | - Brian T Garibaldi
- Division of Pulmonary and Critical Care, Johns Hopkins
University School of Medicine, Baltimore Maryland
| | - Scott L Zeger
- Department of Biostatistics Johns Hopkins University
Bloomberg School of Public Health, Baltimore Maryland
- Correspondence to Dr. Scott Zeger, MD PhD Department of
Biostatistics, 615 N. Wolfe Street, Room E3650 Johns Hopkins University
Bloomberg School of Public Health Baltimore MD 21205 Phone: 410-502-9054
(e-mail: )
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50
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Chen X, Zheng L, Ye S, Xu M, Li Y, Lv K, Zhu H, Jie Y, Chen YQ. Research on Influencing Factors and Classification of Patients With Mild and Severe COVID-19 Symptoms. Front Cell Infect Microbiol 2021; 11:670823. [PMID: 34490135 PMCID: PMC8418155 DOI: 10.3389/fcimb.2021.670823] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Accepted: 06/25/2021] [Indexed: 01/08/2023] Open
Abstract
Objective To analyze the epidemiological history, clinical symptoms, laboratory testing parameters of patients with mild and severe COVID-19 infection, and provide a reference for timely judgment of changes in the patients’ conditions and the formulation of epidemic prevention and control strategies. Methods A retrospective study was conducted in this research, a total of 90 patients with COVID-19 infection who received treatment from January 21 to March 31, 2020 in the Ninth People’s Hospital of Dongguan City were selected as study subject. We analyzed the clinical characteristics of laboratory-confirmed patients with COVID-19, used the oversampling method (SMOTE) to solve the imbalance of categories, and established Lasso-logistic regression and random forest models. Results Among the 90 confirmed COVID-19 cases, 79 were mild and 11 were severe. The average age of the patients was 36.1 years old, including 49 males and 41 females. The average age of severe patients is significantly older than that of mild patients (53.2 years old vs 33.7 years old). The average time from illness onset to hospital admission was 4.1 days and the average actual hospital stay was 18.7 days, both of these time actors were longer for severe patients than for mild patients. Forty-eight of the 90 patients (53.3%) had family cluster infections, which was similar among mild and severe patients. Comorbidities of underlying diseases were more common in severe patients, including hypertension, diabetes and other diseases. The most common symptom was cough [45 (50%)], followed by fever [43 (47.8%)], headache [7 (7.8%)], vomiting [3 (3.3%)], diarrhea [3 (3.3%)], and dyspnea [1 (1.1%)]. The laboratory findings of patients also included leukopenia [13(14.4%)] and lymphopenia (17.8%). Severe patients had a low level of creatine kinase (median 40.9) and a high level of D-dimer. The median NLR of severe patients was 2.82, which was higher than that of mild patients. Logistic regression showed that age, phosphocreatine kinase, procalcitonin, the lymphocyte count of the patient on admission, cough, fatigue, and pharynx dryness were independent predictors of COVID-19 severity. The classification of random forest was predicted and the importance of each variable was displayed. The variable importance of random forest indicates that age, D-dimer, NLR (neutrophil to lymphocyte ratio) and other top-ranked variables are risk factors. Conclusion The clinical symptoms of COVID-19 patients are non-specific and complicated. Age and the time from onset to admission are important factors that determine the severity of the patient’s condition. Patients with mild illness should be closely monitored to identify those who may become severe. Variables such as age and creatine phosphate kinase selected by logistic regression can be used as important indicators to assess the disease severity of COVID-19 patients. The importance of variables in the random forest further complements the variable feature information.
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Affiliation(s)
- Xiaoping Chen
- College of Mathematics and Statistics & FJKLMAA, Fujian Normal University, Fuzhou, China
| | - Lihui Zheng
- College of Mathematics and Statistics & FJKLMAA, Fujian Normal University, Fuzhou, China
| | - Shupei Ye
- Pulmonary and Critical Care Medicine, The Third People's Hospital of Dongguan City, Dongguan, China
| | - Mengxin Xu
- School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen, China
| | - YanLing Li
- School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen, China
| | - KeXin Lv
- School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen, China
| | - Haipeng Zhu
- Department of Infectious Diseases, The Ninth People's Hospital of Dongguan City, Dongguan, China
| | - Yusheng Jie
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yao-Qing Chen
- School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen, China
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